Substituted pyrazoline compounds, their preparation and use as medicaments

ABSTRACT

The present invention relates to substituted pyrazoline compounds, methods for their preparation, medicaments comprising these compounds as well as their use for the preparation of a medicament for the treatment of humans and animals.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalPatent Application No. 60/705,433, filed Aug. 5, 2005, and EuropeanPatent Application No. 05384018, filed Jul. 15, 2005, each of which ishereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to substituted pyrazoline compounds,methods for their preparation, medicaments comprising these compounds aswell as their use for the preparation of a medicament for the treatmentof humans and animals.

BACKGROUND OF THE INVENTION

Cannabinoids are compounds, which are derived from the cannabis sativaplant which is commonly known as marijuana. The most active chemicalcompound of the naturally occurring cannabinoids is tetrahydrocannabinol(THC), particularly Δ⁹-THC.

These naturally occurring cannabinoids as well as their syntheticanalogues promote their physiological effects via binding to specificG-coupled receptors, the so-called cannabinoid-receptors.

At present, two distinct types of receptors that bind both the naturallyoccurring and synthetic cannabinoids have been identified and cloned.These receptors, which are designated CB₁ and CB₂ are involved in avariety of physiological or pathophysiological processes in humans andanimals, e. g. processes related to the central nervous system, immunesystem, cardiovascular system, endocrinous system, respiratory system,the gastrointestinal tract or to reproduction, as described for example,in Hollister, Pharm. Rev. 38, 1986, 1-20; Reny and Singha, Prog. Drug.Res., 36, 71-114, 1991; Consroe and Sandyk, in Marijuana/Cannabinoids,Neurobiology and Neurophysiology, 459, Murphy L. and Barthe A. Eds., CRCPress, 1992.

Therefore, compounds, which have a high binding affinity for thesecannabinoid receptors and which are suitable for modulating thesereceptors are useful in the prevention and/or treatment ofcannabinoid-receptor related disorders.

In particular, the CB₁-receptor is involved in many differentfood-intake related disorders such as bulimia or obesity, includingobesity associated with type II diabetes (non-insulin-dependentdiabetes) and thus, compounds suitable for regulating this receptor maybe used in the prophylaxis and/or treatment of these disorders.

SUMMARY OF THE INVENTION

Thus, it was an object of the present invention to provide novelcompounds for use as active substances in medicaments. In particular,these active substances should be suitable for the modulation ofcannabinoid receptors, more particularly for the modulation ofcannabinoid 1 (CB₁) receptors.

Said object was achieved by providing the substituted pyrazolinecompounds of general formula I given below, their stereoisomers,corresponding salts and corresponding solvates thereof.

It has been found that these compounds have a high affinity forcannabinoid receptors, particularly for the CB₁-receptor, and that theyact as modulators e. g. antagonists, inverse agonists or agonists onthese receptors. They are therefore suitable for the prophylaxis and/ortreatment of various disorders related to the central nervous system,the immune system, the cardiovascular system, the endocrinous system,the respiratory system, the gastrointestinal tract or reproduction inhumans and/or animals, preferably humans including infants, children andgrown-ups.

DETAILED DESCRIPTION OF THE INVENTION

Thus, in one of its aspects the present invention relates to substitutedpyrazoline compounds of general formula I,

wherein

R¹ represents an unsubstituted or at least mono-substituted phenylradical;

R² represents an unsubstituted or at least mono-substituted phenylradical;

R³ represents an unsubstituted or at feast mono-substituted radicalselected from the group consisting of cyclononyl, cyclononyl,cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl, aziridinyl,azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl,tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl. (3,4)dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopentat[c]pyrrolyl,(1,3,4,1,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, 9H-carbazolyl,decahydroisoquinolinyl, (6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopentat[b]-indolyl,

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —C₁₋₆-alkyl substituted withone or more hydroxy groups, —C₁₋₆-alkyl substituted with one or morechlorine atoms, —C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —O—C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, —O—C(═O)—C₁₋₆-alkyl,—SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—C₁₋₆-alkyl,—N(C₁₋₆-alkyl)-C(═O)-C₁₋₆-alkyl, —CHO, —C(═O)—C₁₋₆-perfluoroalkyl,—C(═S)—NH—C₁₋₆-alkyl, —CF₂H, —CFH₂, —C(═O)—NH—NR^(C)R^(D),—S(═O)₂-phenyl, —(C₁₋₅-alkylene)-S—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl,—NR^(A)R^(B), —(C₁₋₅-alkylene)-NR^(A)R^(B), —S(═O)₂—NH—C₁₋₆-alkyl,—S(═O)₂—NH-phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,pyrrolidinyl, piperidinyl, thiophenyl, phenoxy and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, phenyl, pyrrolidinyl, piperidinyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃;

a —NR⁴R⁵ moiety

or a —O—R⁶ moiety;

R⁴ represents a hydrogen atom or a saturated or unsaturated,unsubstituted or at least mono-substituted aliphatic radical;

R⁵ represents an unsubstituted or at least mono-substituted radicalselected from the group consisting of 2-pentyl, 3-pentyl, neo-pentyl,2-hexyl, 3-hexyl, 2-heptyl, 3-heptyl, 4-heptyl, 2-octyl, 3-octyl,4-octyl, 2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl, 2-(5-methyl )-hexyl,2-(4-methyl )-hexyl, 2-(7-methyl)-octyl, 2-(6-methyl)-octyl, —O-methyl,—O-ethyl, —O-n-propyl, —O-isopropyl, —O-n-butyl, —O-isobutyl,—O-tert-butyl, —O-n-pentyl and —O-n-hexyl;

a substituted radical selected from the group consisting of methyl,ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl,n-hexyl, n-heptyl and n-octyl, which is substituted with 1, 2, 3, 4, 5,6, 7, 8 or 9 substituents independently selected from the groupconsisting of —NH—C₁₋₆-alkyl, —N(C₁₋₆-alkyl)₂, —C(═O)—O—C₁₋₆-alkyl and—NH—C(═O)—C₁₋₆-alkyl;

an unsubstituted or at least mono-substituted radical selected from thegroup consisting of adamantyl, cyclononyl, cyclodecyl, cycloundecyl,cyclododecyl, cyclotridecyl, cyclotetradecyl, aziridinyl, azetidinyl,imidazolidinyl, thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl,tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl, (1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl, dodecahydro-carbazolyl,9H-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —C₁₋₆-alkyl substituted withone or more hydroxy groups, —C₁₋₆-alkyl substituted with one or morechlorine atoms, —C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —O—C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, —O—C(═O)—C₁₋₆-alkyl,—SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—C₁₋₆-alkyl,—N(C₁₋₆-alkyl)-C(═O)—C₁₋₆-alkyl, —CHO, —C(═O)—C₁₋₆-perfluoroalkyl,—C(═S)—NH—C₁₋₆-alkyl, —CF₂H, —CFH₂, —C(═O)—NH—NR^(C)R^(D),—S(═O)₂-phenyl, —(C₁₋₅-alkylene)-S—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl,—NR^(A)R^(B), —(C₁₋₅-alkylene)-NR^(A)R^(B), —S(═O)₂—NH—C₁₋₆-alkyl,—S(═O)₂—NH-phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,pyrrolidinyl, piperidinyl, thiophenyl, phenoxy, —O-Benzyl, and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, phenyl, cyclohexyl, pyrrolidinyl, piperidinyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃;

a saturated or unsaturated, unsubstituted or at least mono-substituted,optionally at least one heteroatom as a ring member containingcycloaliphatic radical, which is bonded via an unsubstituted or at leastmono-substituted alkylene group, alkenylene group or alkinylene groupmay be condensed with an unsubstituted or at least mono-substitutedmono- or polycyclic ring system and/or may be bridged by at least oneunsubstituted or at least mono-substituted alkylene group;

a —NR⁷R⁸ moiety; a —P(═O)(OR⁹)₂ moiety; a —C(═O)—OR¹⁰ moiety; a —C(═O)—NH—R¹¹ moiety or a —C(═O)—R¹² moiety;

R⁶ represents an unsubstituted or at least mono-substituted C₅₋₁₆alkylradical, C₂₋₁₆ alkenyl radical or C₂₋₁₆ alkinyl radical;

or a saturated or unsaturated, unsubstituted or at leastmono-substituted, optionally at least one heteroatom as a ring membercontaining cycloaliphatic radical, which may be condensed with anunsubstituted or at least mono-substituted mono- or polycyclic ringsystem and/or may be bridged by at least one unsubstituted or at leastmono-substituted alkylene group;

a —P(═O)(OR⁹)₂ moiety; a —C(═O)—OR¹⁰ moiety; a —C(═O)—NH—R¹¹ moiety or a—C(═O)—R¹² moiety.

R⁷ represents a hydrogen atom or a saturated or unsaturated,unsubstituted or at least mono-substituted aliphatic radical;

R⁸ represents an unsubstituted or at least mono-substituted radicalselected from the group consisting of 2-pentyl, 3-pentyl, neo-pentyl,2-hexyl, 3-hexyl, 2-heptyl, 3-heptyl, 4-heptyl, 2-octyl, 3-octyl,4-octyl, 2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl, 2-(5-methyl)-hexyl,2-(4-methyl)-hexyl, 2-(7-methyl)-octyl, 2-(6-methyl)-octyl, —O-methyl,—O-ethyl, —O-n-propyl, —O-isopropyl, —O-n-butyl, —O-isobutyl,—O-tert-butyl, —O-n-pentyl and —O-n-hexyl;

a substituted radical selected from the group consisting of methyl,ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl,n-hexyl, n-heptyl and n-octyl, which is substituted with 1, 2, 3, 4, 5,6, 7, 8 or 9 substituents independently selected from the groupconsisting of —NH—C₁₋₆-alkyl, —N(C₁₋₆-alkyl)₂, —C(═O)—O—C₁₋₆-alkyl and—NH—C(═O)—C₁₋₆-alkyl;

an unsubstituted or at least mono-substituted radical selected from thegroup consisting of cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —C₁₋₆-alkyl substituted withone or more hydroxy groups, —C₁₋₆-alkyl substituted with one or morechlorine atoms, —C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —O—C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, —O—C(═O)—C₁₋₆alkyl,—SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—C₁₋₆-alkyl,—N(C₁₋₆-alkyl)-C(═O)—C₁₋₆-alkyl, —CHO, —C(═O)—C₁₋₆-perfluoroalkyl,—C(═S)—NH—C₁₋₆-alkyl, —CF₂H, —CFH₂, —C(═O)—NH—NR^(C)R^(D),—S(═O)₂-phenyl, —(C₁₋₅-alkylene)-S—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl,—NR^(A)R^(B), —(C₁₋₅-alkylene)-NR^(A)R^(B), —S(═O)₂—NH—C₁₋₆-alkyl,—S(═O)₂—NH-phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,pyrrolidinyl, piperidinyl, thiophenyl, phenoxy and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, phenyl, pyrrolidinyl, piperidinyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃;

or a saturated or unsaturated, unsubstituted or at leastmono-substituted, optionally at least one heteroatom as a ring membercontaining cycloaliphatic radical, which is bonded via an unsubstitutedor at least mono-substituted alkylene group, alkenylene group oralkinylene group may be condensed with an unsubstituted or at leastmono-substituted mono- or polycyclic ring system and/or may be bridgedby at least one unsubstituted or at least mono-substituted alkylenegroup;

R⁹, R¹⁰, R¹¹ and R¹², independently of one another, in each caserepresent a saturated or unsaturated, unsubstituted or at leastmono-substituted aliphatic radical;

or an unsubstituted or at least mono-substituted aryl or heteroarylradical, which may be condensed with an unsubstituted or at leastmono-substituted mono- or polycyclic ring system and/or may be bondedvia an unsubstituted or at least mono-substituted alkylene group,alkenylene group or alkinylene group;

R^(A) and R^(B), independently of one another, in each case represent—C₁₋₆-alkyl or R^(A) and R^(B) in each case together with the bridgingnitrogen atom form a radical selected from the group consisting ofpyrrolidinyl, imidazolidinyl, piperazinyl, piperidinyl, thiomorpholinyl,morpholinyl, azepanyl and diazepanyl which may be at leastmono-substituted with one or more identical or different C₁₋₆ alkylradicals; and

R^(C) and R^(D), independently of one another, in each case representhydrogen, —C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, C₃₋₈cycloalkyl,—(C₁₋₅-alkylene)-C₃₋₈-cycloalkyl, —(C₁₋₆-alkylene)-O—C₁₋₆-alkyl or—C₁₋₆-alkyl substituted with one or more hydroxy groups or R^(C) andR^(D) in each case together with the bridging nitrogen atom form aradical selected from the group consisting of pyrrolidinyl,imidazolidinyl, piperazinyl, piperidinyl, thiomorpholinyl, morpholinyl,azepanyl and diazepanyl which may be at least mono-substituted with oneor more substituents independently selected from the group consisting—C₁₋₆-alkyl, —C(═O)—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl,—C(═O)—NH—C₁₋₆-alkyl, —C(═S)—NH—C₁₋₆-alkyl, oxo (═O), —C₁₋₆-alkylsubstituted with one or more hydroxy groups.—(C₁₋₆-alkylene)-O—C₁₋₆-alkyl and —C(═O)—NH₂;

optionally in form of one of its stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofits stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding N-oxide thereof, or a physiologicallyacceptable salt thereof, or a corresponding solvate thereof.

If one or more of the residues R¹ to R¹² and R^(A), R^(B), R^(C) andR^(D) represents or comprises an aryl, phenyl or heteroaryl radical,which may be substituted, unless defined otherwise, preferably saidaryl, phenyl or heteroaryl radical may optionally be substituted with 1,2, 3, 4 or 5 substituent(s) independently selected from the groupconsisting of C₁₋₆-perfluoralkyl, —C₁₋₆-alkyl substituted with one ormore methoxy and/or ethoxy groups, —C₁₋₆-alkyl, —C₁₋₆-alkyl substitutedwith one or more hydroxy groups, —C₁₋₆-alkyl substituted with one ormore chlorine atoms, —O—C₁₋₆-alkyl, —O—C₁₋₆-alkyl substituted with oneor more methoxy and/or ethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—OH,—C(═O)—O—C₁₋₆-alkyl, —O—C(═O)—C₁₋₆-alkyl, F, Cl, Br, I, —CN, —OCF₃,—O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₃, —SCH₂, —OH, —SH, —SO₃H,—NH—C(═O)—C₁₋₆-alkyl, —N(C₁₋₆-alkyl)-C(═O)—C₁₋₆-alkyl, —NO₂, —CHO,—C(═O)—C₁₋₆-alkyl, —C(═O)—C₁₋₆-perfluoroalkyl, —C(═S)—NH—C₁₋₆-alkyl,—CF₂H, —CFH₂, —C(═O)—NR^(K)R^(L), —C(═O)—NH—NR^(G)R^(H),—S(═O)—C₁₋₆-alkyl, —S(═O)₂—C₁₋₆-alkyl, —S(═O)₂-phenyl,—(C₁₋₅-alkylene)-S—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)—C₁₋₆alkyl,—(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl, —NR^(E)R^(F),—(C₁₋₅-alkylene)-NR^(E)R^(F), —S(═O)—NH₂, —S(═O)₂—NH—C₁₋₆-alkyl,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—C₁₋₆-alkyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl,phenoxy and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃ and

whereby R^(K), R^(L), R^(E) and R^(F), independently of one another,represent hydrogen or —C₁₋₆-alkyl or R^(K) and R^(L) in each casetogether with the bridging nitrogen atom form a radical selected fromthe group consisting of pyrrolidinyl, imidazolidinyl, piperazinyl,piperidinyl, thiomorpholinyl, morpholinyl, azepanyl and diazepanyl whichmay be at least mono-substituted with one or more identical or differentC₁₋₆-alkyl radicals

and whereby R^(G) and R^(H), independently of one another, representhydrogen, —C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, C₃₋₈-cycloalkyl,—(C₁₋₅-alkylene)-C₃₋₈-cycloalkyl, —(C₁₋₆-alkylene)-O—C₁₋₆-alkyl or—C₁₋₆-alkyl substituted with one or more hydroxy groups or R^(G) andR^(H) in each case together with the bridging nitrogen atom form aradical selected from the group consisting of pyrrolidinyl,imidazolidinyl, piperazinyl, piperidinyl, thiomorpholinyl, morpholinyl,azepanyl and diazepanyl which may be at least mono-substituted with oneor more substituents independently selected from the group consisting—C₁₋₆-alkyl, —C(═O)—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl,—C(═O)—NH—C₁₋₆-alkyl, —C(═S)—NH—C₁₋₆-alkyl, oxo (═O), —C₁₋₆-alkylsubstituted with one or more hydroxy groups,—(C₁₋₆-alkylene)-O—C₁₋₆-alkyl and —C(═O)NH₂.

More preferably said phenyl, aryl and heteroaryl radicals may optionallybe substituted with 1, 2, 3, 4 or 5 substituent(s) independentlyselected from the group consisting of —CF₃, —C₂F₅, —C₃F₇, —C₄F₉, —CH₂Cl,—CHCl₂, —C₂H₄Cl, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,2-butyl, tert-butyl, n-pentyl, 2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH,—CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃, —O—CH₂—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅,—C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂, —O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃,—O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —S—CH₃, —S—C₂H₅,—S—CH₂—CH₂CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃,—O—C(═O)—C(CH₃)₃, F, Cl, Br, I, —CH, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉,—SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅,—NH—C(═O)—C(CH₃)₃, —NO₂, —CHO, —C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃,—C(═O)—CF₃, —C(═O)—C₂F₅, —C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅,—CF₂H, —CFH₂, —C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅,—C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇,—S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —S(═)₂-phenyl, —NH₂, —NH—CH₃,—NH—C₂H₅, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby said thiophenyl radical can be substituted with 1, 2 or3 substituent(s) independently selected from the group consisting of F,Cl, Br, methyl, ethyl and n-propyl.

Preferred aryl radicals which are optionally at least mono-substitutedare phenyl and naphthyl (1- and 2-naphthyl).

Preferably the heteroatoms which are present as ring members in theheteroaryl radical may, unless defined otherwise, independently beselected from the group consisting of nitrogen, oxygen and sulfur. Morepreferably a heteroaryl radical is 5- to 14-membered and may comprise 1,2, 3 or 4 heteroatoms independently selected from the group consistingof nitrogen, oxygen and sulfur.

Preferred heteroaryl radicals which are unsubstituted or at leastmono-substituted are pyridinyl, furyl(furanyl), thienyl(thiophenyl),pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl,pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridazinyl, indolyl,isoindolyl, pyrimidinyl, pyrazinyl, quinolinyl, isoquinolinyl,benzo[b]furanyl, benzo[b]thiophenyl, benzo[2,1,3]thiadiazolyl,[1,2,3]-benzothiadiazolyl, [2,1,3]-benzoxadiazolyl,[1,2,3]-benzoxadiazolyl, benzoxazolyl, benzthiazolyl, benzisoxazolyl,benzisothiazolyl, imidazo[2,1-b]thiazolyl, 2H-chromenyl, pyranyl,indazolyl and quinazolinyl.

Preferred aryl and heteroaryl radicals which are condensed with a mono-or polycyclic ring system are [1,3]-benzodioxolyl, [1,4]-benzodioxanyl,[1,2,3,4]-tetrahydronaphthyl, (2,3)-dihydro-1H-cyclopenta[b]indolyl,[1,2,3,4]-tetrahydroquinolinyl, [1,2,3,4]-tetrahydroisoquinolinyl,[1,2,3,4]-tetrahydroquinazolinyl and[3,4]-dihydro-2H-benzo[1,4]oxazinyl.

If one or more of the residues R¹ to R¹² or R^(A), R^(B), R^(C) andR^(D) represents or comprises a saturated or unsaturated, optionally atleast one heteroatom as a ring member containing cycloaliphatic radical,preferably a C₃₋₁₈ cycloaliphatic radical, a heterocyclic ring,preferably a 4- to 10-membered heterocyclic ring, a C₃₋₁₆, cycloalkylradical, a C₄₋₁₆ cycloalkenyl radical, a C₄₋₁₆ heterocycloalkyl radical,or a C₅₋₁₆ heterocycloalkenyl radical, which may be substituted, unlessdefined otherwise, preferably said cycloaliphatic radical, heterocyclicring, C₃₋₁₆ cycloalkyl radical, C₄₋₁₆ cycloalkenyl radical, C₄₋₁₆heterocycloalkyl radical, or C₅₋₁₆ heterocycloalkenyl radical, may ineach case optionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of oxo (═O), thioxo(═S), C₁₋₆-perfluoralkyl, —C₁₋₆-alkyl, —C₁₋₆-alkyl substituted with oneor more hydroxy groups, —C₁₋₆-alkyl substituted with one or morechlorine atoms, —C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —O—C₁₋₆-alkyl, —O—C₁₋₆-alkyl substituted with one or moremethoxy and/or ethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—OH,—C(═O)—O—C₁₋₆-alkyl, —O—C(═O)—C₁₋₆-alkyl, F, Cl, Br, I, —CN, —OCF₃,—O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —SO₃H,—NH—C(═O)—C₁₋₆-alkyl, —N(C₁₋₆-alkyl)-C(═O)—C₁₋₆-alkyl, —NO₂, —CHO,—C(═O)—C₁₋₆-alkyl, —C(═O)—C₁₋₆-perfluoroalkyl, —C(═S)—NH—C₁₋₆-alkyl,—CF₂H, —CFH₂, —C(═O)NR^(K)R^(L), —C(═O)—NH—NR^(G)R^(H),—S(═O)—C₁₋₆-alkyl, —S(═O)₂—C₁₋₆-alkyl, —S(═O)₂-phenyl,—(C₁₋₅-alkylene)S—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)₂—C₁₋₅-alkyl, —NR^(E)R^(F),—(C₁₋₅-alkylene)-NR^(E)R^(F), —S(═O)—NH₂, —S(═O)₂—NH—C₁₋₆-alkyl,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—C₁₋₆alkyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl,phenoxy and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃ and

whereby R^(K), R^(L), R^(E) and R^(F), independently of one another,represent hydrogen or —C₁₋₆-alkyl or R^(K) and R^(L) in each casetogether with the bridging nitrogen atom form a radical selected fromthe group consisting of pyrrolidinyl, imidazolidinyl, piperazinyl,piperidinyl, thiomorpholinyl, morpholinyl, azepanyl and diazepanyl whichmay be at least mono-substituted with one or more identical or differentC₁₋₆ alkyl radicals

and whereby R^(G) and R^(H), independently of one another, representhydrogen, —C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, C₃₋₈-cycloalkyl,—(C₁₋₅-alkylene)-C₃₋₈-cycloalkyl, —(C₁₋₆-alkylene)-O—C₁₋₆-alkyl or—C₁₋₆-alkyl substituted with one or more hydroxy groups or R^(G) andR^(H) in each case together with the bridging nitrogen atom form aradical selected from the group consisting of pyrrolidinyl,imidazolidinyl, piperazinyl, piperidinyl, thiomorpholinyl, morpholinyl,azepanyl and diazepanyl which may be at least mono-substituted with oneor more substituents independently selected from the group consisting—C₁₋₆-alkyl, —C(═O)—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl,—C(═O)—NH—C₁₋₆-alkyl, —C(═S)—NH—C₁₋₆-alkyl, oxo (═O), —C₁₋₆-alkylsubstituted with one or more hydroxy groups,—(C₁₋₆-alkylene)-O—C₁₋₆-alkyl and —C(═O)—NH₂.

More preferably said cycloaliphatic radicals, heterocyclic rings, C₃₋₁₆cycloalkyl radicals, C₄₋₁₆ cycloalkenyl radicals, C₄₋₁₆ heterocycloalkylradicals, or C₅₋₁₆ heterocycloalkenyl radicals may optionally besubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of oxo (═O), thioxo (═S), —CF₃, —C₂F₅, —C₃F₇,—C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl, 2-pentyl, n-hexyl,—CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃, —O—CH₂—CH₂—O—CH₃,—O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —S—CH₃,—S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—CH₂H₅, —C(═O)—O—C₃H₇,—C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂,—O—C(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, F, Cl, Br, I, —CN, —OCF₃,—O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —SO₃H,—NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═)—C(CH₃)₃, —NO₂, —CHO, —C(═O)—CH₃,—C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—CF₃, —C(═O)—C₂F₅, —C(═O)—C₃F₇,—C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅, —CF₂H, —CFH₂, —C(═O)—NH₂, —C(═O)—NH—CH₃,—C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂,—C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂,—S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃, —S(═O)₂—C₂H₅,—S(═O)₂—C₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃, —NH—C₂H₅, —N(CH₃)₂,—N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl, —(CH₂)-piperidinyl,—(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂, —CH₂—N(C₄H₉)₂,—CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃, —S(═O)₂—NH-phenyl,—NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy and benzyl,whereby said thiophenyl radical can be substituted with 1, 2 or 3substituents independently selected from the group consisting of F, Cl,Br, methyl, ethyl and n-propyl.

If one or more of the residues R¹ to R¹² or R^(A), R^(B), R^(C) andR^(D) represents or comprises a cycloaliphatic radical, preferably aC₃₋₁₆ cycloaliphatic radical, which contains one or more heteroatoms asring members, unless defined otherwise, each of these heteroatoms maypreferably be selected from the group consisting of nitrogen, oxygen andsulfur. More preferably a cycloaliphatic group may optionally contain 1,2, 3 or 4 heteroatom(s) independently selected from the group consistingof N, O and S as ring members.

Suitable saturated or unsaturated, optionally at least one heteroatom asring member containing cycloaliphatic radicals may preferably beselected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl,cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl, morpholinyl, aziridinyl,azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl,tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl and (1,3)-dioxolanyl.

Suitable saturated or unsaturated, optionally at least one heteroatom asring member containing cycloaliphatic radicals which are condensed withan unsubstituted or at least mono-substituted mono- or polycyclic ringsystem may preferably be selected from the group consisting ofindolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,(1,2,3,4)-tetrahydronaphthyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl and(1,2,3,4)-tetrahydroquinoxazlinyl.

Preferably a cycloaliphatic radical, a C₃₋₁₆ cycloalkyl radical, a C₄₋₁₆cycloalkenyl radical, a C₄₋₁₆ heterocycloalkyl radical or a C₅₋₁₆heterocycloalkenyl radical may be bridged by 1, 2 or 3 unsubstituted orat least mono-substituted alkylene group(s).

Suitable saturated or unsaturated, optionally at least one heteroatom asring member containing cycloaliphatic radicals which are bridged by atleast one unsubstituted or at least mono-substituted alkylene group maypreferably be selected from the group consisting of adamantyl,bicyclo[2.2.1 ]heptyl, bicyclo[3.1.1]heptyl, norbornenyl and8-aza-bicyclo[3.2.1]octyl.

A suitable saturated or unsaturated, optionally at least one heteroatomas ring member containing cycloaliphatic radical which together with asaturated or unsaturated, unsubstituted or at least mono-substitutedcycloaliphatic radical forms a spirocyclic residue via a common ringatom is 8-aza-spiro[4.5]decanyl.

A mono- or polycyclic ring system according to the present invention—ifnot defined otherwise—means a mono- or polycyclic hydrocarbon ringsystem, preferably a mono- or bicyclic ring system, that may besaturated, unsaturated or aromatic. Each of its different rings may showa different degree of saturation, i.e. they may be saturated,unsaturated or aromatic. Optionally each of the rings of the mono- orbicyclic ring system may contain one or more, preferably 1, 2 or 3,heteroatom(s) as ring member(s), which may be identical or different andwhich can preferably be selected from the group consisting of nitrogen,oxygen and sulfur. The rings of the mono- or bicyclic ring system arepreferably 5-, 6- or 7-membered.

The term “condensed” according to the present invention means that aring or ring system is attached to another ring or ring system, wherebythe terms “annulated” or “annelated” are also used by those skilled inthe art to designate this kind of attachment.

If one or more of the residues R¹ to R¹² comprises a mono- or polycyclicring system, which may be substituted, unless defined otherwise,preferably said mono- or polycyclic ring system may optionally besubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of oxo (═O), thioxo (═S), C₁₋₆-perfluoralkyl,—C₁₋₆-alkyl, —C₁₋₆-alkyl substituted with one or more hydroxy groups,—C₁₋₆-alkyl substituted with one or more chlorine atoms, —C₁₋₆-alkylsubstituted with one or more methoxy and/or ethoxy groups,—O—C₁₋₆-alkyl, —O—C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—OH, —C(═O)—O—C₁₋₆-alkyl,—O—C(═O)—C₁₋₆-alkyl, F, Cl, Br, I, —CN, —OCF₃, —O—C₂F₅, —O—C₃F₇,—O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —SO₃H, —NH—C(═O)—C₁₋₆-alkyl,—N(C₁₋₆-alkyl)-C(═O)—C₁₋₆-alkyl, —NO₂, —CHO, —C(═O)—C₁₋₆-alkyl,—C(═O)—C₁₋₆-perfluoroalkyl, —C(═S)—NH—C₁₋₆-alkyl, —CF₂H, —CFH₂,—C(═O)—R^(K)R^(L), —C(═O)—NH—NR^(G)R^(H), —S(═O)—C₁₋₆-alkyl,—S(═O)₂—C₁₋₆-alkyl, —S(═O)₂-phenyl, —(C₁₋₅-alkylene-S—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl,—NR^(E)R^(F), —(C₁₋₆-alkylene)-NR^(E)R^(F), S(═O)—NH₂,—S(═O)₂—NH—C₁₋₆-alkyl, —S(═O)₂—NH-phenyl, —NH—S(═O)₂—C₁₋₆-alkyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl,piperidinyl, phenyl, thiophenyl, phenoxy and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, I, —OH, —CF₃, —CN, —NO₂, C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃ and

whereby R^(K), R^(L), R^(E) and R^(F), independently of one another,represent hydrogen or —C₁₋₆-alkyl or R^(K) and R^(L) in each casetogether with the bridging nitrogen atom form a radical selected fromthe group consisting of pyrrolidinyl, imidazolidinyl, piperazinyl,piperidinyl, thiomorpholinyl, morpholinyl, azepanyl and diazepanyl whichmay be at least mono-substituted with one or more identical or differentC₁₋₆ alkyl radicals

and whereby R^(G) and R^(H), independently of one another, representhydrogen, —C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, C₃₋₈-cycloalkyl,—(C₁₋₅-alkylene)-C₃₋₈-cycloalkyl, —(C₁₋₆-alkylene)-O—C₁₋₆-alkyl or—C₁₋₆-alkyl substituted with one or more hydroxy groups or R^(G) andR^(H) in each case together with the bridging nitrogen atom form aradical selected from the group consisting of pyrrolidinyl,imidazolidinyl, piperazinyl, piperidinyl, thiomorpholinyl, morpholinyl,azepanyl and diazepanyl which may be at least mono-substituted with oneor more substituents independently selected from the group consisting—C₁₋₆-alkyl, —C(═O)—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl,—C(═O)—NH—C₁₋₆-alkyl, —C(═S)—NH—C₁₋₆-alkyl, oxo (═O), —C₁₋₆-alkylsubstituted with one or more hydroxy groups,—(C₁₋₆-alkylene)-O—C₁₋₆-alkyl and —C(═O)—NH₂.

More preferably said mono- or polycyclic ring system may optionally besubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of oxo (═O), thioxo (═S), —CF₃, —C₂F₅, —C₃F₇,—C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl, 2-pentyl, n-hexyl,—CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃, —O—CH₂—CH₂—O—CH₃,—O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—OH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —S—CH₃,—S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃,—O—C(═O)—C(CH₃)₃, F, Cl, Br, I, —CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉,—SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅,—NH—C(═O)—C(CH₃)₃, —NO₂, —CHO, —C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃,—C(═O)—CF₃, —C(═O)—C₂F₅, —C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅,—CF₂H, —CFH₂, —C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅,—C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇,—S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)—CH₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃,—NH—C₂H₅, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby said thiophenyl radical can be substituted with 1, 2 or3 substituents independently selected from the group consisting of F,Cl, Br, methyl, ethyl and n-propyl.

If one or more of the residues R⁴ to R¹² represent or comprise asaturated or unsaturated, unsubstituted or at least mono-substitutedaliphatic radical, preferably a C₁₋₆ aliphatic radical, said aliphaticradical may be linear or branched.

Preferably aliphatic radicals, C₁₋₁₆ alkyl radicals, C₂₋₁₆ alkenylradical and C₂₋₁₆ alkinyl radicals, unless defined otherwise, mayoptionally be substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 substituentsindependently selected from the group consisting of —OH, F, Cl, Br, I,—O—C₁₋₆-alkyl, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —CF₃, —C₂F₅, —C₃F₇,—C₄F₉, —NH₂, —NH—C₁₋₆-alkyl, —N(C₁₋₆-alkyl)₂, —C(═O)—OH,—C(═O)—O—C₁₋₆-alkyl, —C(═O)—NH₂, —C(═O)—NH—C₁₋₆-alkyl,—C(═O)—N(C₁₋₆alkyl)₂, —CN, —NO₂, —S(═O)—NH₂, —CHO, —C(═O)—C₁₋₆-alkyl,—S(═O)—C₁₋₆-alkyl, —S(═O)₂—C₁₋₆-alkyl, —NH—S(═O)—C₁₋₆-alkyl,—NH—C(═O)—O—C₁₋₆-alkyl and —NH—C(═O)—C₁₋₆-alkyl.

More preferably aliphatic radicals, C₁₋₁₆-alkyl radicals, C₂₋₁₆ alkenylradical and C₂₋₁₆ alkinyl radicals may optionally be substituted with 1,2, 3, 4, 5, 6, 7, 8 or 9 substituents independently selected from thegroup consisting of —OH, F, Cl, Br, I, —O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃,—O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, —CN, —NO₂, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅,—NH—C(═O)—C(CH₃)₃, —NH—C(═O)—O—CH₃, —NH—C(═O)—O—C₂H₅,—NH—C(═O)—O—C(CH₃)₃, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C(CH₃)₃,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C(CH₃)₃, —C(═O)—CH₃, —C(═O)—C₂H₅ and —C(═O)—C(CH₃)₃.

Suitable alkyl radicals, preferably C₁₋₁₆ alkyl radicals, are selectedfrom the group consisting of methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl,neo-pentyl, n-hexyl, 2-hexyl, 3-hexyl, n-heptyl, 2-heptyl, 3-heptyl,4-heptyl, n-octyl, 2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl,2-(5-methyl)-heptyl, 2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl,2-(7-methyl)-octyl, 2-(6-methyl)-octyl, n-nonyl, n-decyl, n-undecyl,n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecycl and n-hexadecyl.

Suitable at least mono-substituted alkyl radicals are selected from thegroup consisting of —CF₃, —CH₂F, —CF₂H, —CH₂—O—CH₃, —C₂F₅, —CH₂—CH₂—F,—CH₂—CN, —CH₂—OH, —CH₂—CH₂—CN, —CH₂—CH₂—OH, —CH₂—CH₂—OCH₃,—CH₂—CH₂—CH₂—CN, —CH₂—CH₂—CH₂—OH, —CH₂—CH₂—CH₂—O—CH₃,—CH₂—CH₂—CH₂—CH₂—O—CH₃, —CH₂—NH₂, —CH₂—N(CH₃)₂, —CH₂—N(C₂H₅)₂,—CH₂—CH—NH₂, —CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂, —CH₂—CH₂—CH₂—NH₂,—CH₂—CH₂—CH₂—N(CH₃)₂ and —CH₂—CH₂—CH₂—N(C₂H₅)₂.

An alkenyl radical according to the present invention comprises at leastone carbon-carbon double bond. Suitable alkenyl radicals, preferablyC₂₋₁₆ alkenyl radicals, are selected from the group consisting of vinyl,n-propenyl, n-butenyl, n-pentenyl, n-hexenyl, n-heptenyl, n-octenyl,n-nonenyl, n-decenyl, n-undecenyl, n-dodecenyl, n-tridecenyl,n-tetradecenyl, n-pentadecenyl and n-hexadecenyl.

An alkinyl radical comprises at least one carbon-carbon triple bond.Suitable alkinyl radicals, preferably C₂₋₁₆ alkinyl radicals, areselected from the group consisting of ethinyl, propinyl, n-butinyl,n-pentinyl, n-hexinyl, n-octinyl, n-noninyl, n-decinyl, n-undecinyl,n-dodecinyl, n-tridecinyl, n-tetradecinyl, n-pentadecinyl andn-hexadecinyl.

If any of the substituents represents an alkylene group, an alkenylenegroup or an alkinylene group, which may be substituted, said alkylenegroup, alkenylene group or alkinylene group may—if not definedotherwise—be unsubstituted or substituted by one or more substituents,preferably unsubstituted or substituted with 1, 2 or 3 substituent(s).Said substituent(s) may preferably be selected independently from thegroup consisting of —O—C₁₋₆-alkyl, —S—C₁₋₆-alkyl, —F, Cl, Br, I, —CN,—CF₃, —OCF₃, —SCF₃, —OH, —SH, —SO₃H, —NH₂, —NH(C₁₋₆-alkyl),—N(C₁₋₆-alkyl)₂ and phenyl. More preferably said substituent(s) may beselected from the group consisting of —F, Cl, Br, I, —CN, —CF₃, —OCF₃,—SCF₃, —OH, —SH, —SO₃H, —NH₂, —NH—CH₃, —N(CH₃)₂, —O—CH₃ and —O—C₂H₅. Analkenylene group comprises at least one carbon-carbon double bond, analkinylene group comprises at least one carbon-carbon triple bond.

Suitable alkylene groups, preferably C₁₋₅-alkylene groups, include—(CH₂)—, —CH(CH₃)—, —CH(phenyl), —(CH₂)₂—, —(CH₂)₃—, —(CH₂)₄—, —(CH₂)₅and —(CH₂)₆—, suitable alkenylene groups, preferably C₂₋₅-alkenylenegroups, include —CH═CH—, —CH₂—CH═CH— and —CH═CH—CH₂— and suitablealkinylene groups, preferably C₂₋₆-alkinylene groups, include —C═C—,—CH₂—C═C— and —C═C—CH₂—.

Preferred are substituted pyrazoline compounds of general formula Igiven above wherein

R¹ represents an unsubstituted or at least mono-substituted phenylradical;

R² represents an unsubstituted or at least mono-substituted phenylradical;

R³ represents an unsubstituted or at least mono-substituted radicalselected from the group consisting of cyclononyl, cyclodecyl,cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl, aziridinyl,azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl,tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —C₁₋₆-alkyl substituted withone or more hydroxy groups, —C₁₋₆-alkyl substituted with one or morechlorine atoms, —C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —O—C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, —O—C(═O)—C₁₋₆-alkyl,—SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—C₁₋₆-alkyl,—N(C₁₋₆-alkyl)-C(═O)—C₁₋₆-alkyl, —CHO, —C(═O)—C₁₋₆-perfluoroalkyl,—O(═S)—NH—C₁₋₆-alkyl, —CF₂H, —CFH₂, —C(═O)—NH—NR^(C)R^(D),—S(═O)₂-phenyl, —(C₁₋₅-alkylene)-S—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl,—NR^(A)R^(B), —(C₁₋₅-alkylene)-NR^(A)R^(B), —S(═O)₂—NH—C₁₋₆-alkyl,—S(═O)₂—NH-phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,pyrrolidinyl, piperidinyl, thiophenyl, phenoxy and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, phenyl, pyrrolidinyl, piperidinyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃,

a —NR⁴R⁵ moiety

or a —O—R⁶ moiety;

R⁴ represents a hydrogen atom or an unsubstituted or at leastmono-substituted C₁₋₆ alkyl radical, C₂₋₁₆ alkenyl radical or C₂₋₁₆alkinyl radical;

R⁵ represents an unsubstituted or at least mono-substituted radicalselected from the group consisting of 2-pentyl, 3-pentyl, neo-pentyl,2-hexyl, 3-hexyl, 2-heptyl, 3-heptyl, 4-heptyl, 2-octyl, 3-octyl,4-octyl, 2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl, 2-(5-methyl )-hexyl,2-(4-methyl)hexyl, 2-(7-methyl)-octyl, 2-(6-methyl )-octyl, —O-methyl;—O-ethyl, —O-n-propyl, —O-isopropyl, —O-n-butyl, —O-isobutyl,—O-tert-butyl, —O-n-pentyl and —O-n-hexyl;

a substituted radical selected from the group consisting of methyl,ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl,n-hexyl, n-heptyl and n-octyl, which is substituted with 1, 2, 3, 4, 5,6, 7, 8 or 9 substituents independently selected from the groupconsisting of —NH—C₁₋₆-alkyl, —N(C₁₋₆-alkyl)₂, —C(═O)—O—C₁₋₆-alkyl and—NH—C(═O)—C₁₋₆-alkyl;

an unsubstituted or at least mono-substituted radical selected from thegroup consisting of adamantyl, cyclononyl, cyclodecyl, cycloundecyl,cyclododecyl, cyclotridecyl, cyclotetradecyl, aziridinyl, azetidinyl,imidazolidinyl, thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl,tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3,1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —C₁₋₆-alkyl substituted withone or more hydroxy groups, —C₁₋₆-alkyl substituted with one or morechlorine atoms, —C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —O—C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, —O—C(═O)—C₁₋₆-alkyl,—SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—C₁₋₆-alkyl,—N(C₁₋₆-alkyl)-C(═O)—C₁₋₆-alkyl, —CHO, —(═O)—C₁₋₆-perfluoroalkyl,—C(═S)—NH—C₁₋₆-alkyl, —CF₂H, —CFH₂, —C(═O)—NH—NR^(C)R^(D),—S(═O)₂-phenyl, —(C₁₋₅-alkylene)-S—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl,—NR^(A)R^(B), —(C₁₋₅-alkylene)-NR^(A)R^(B), —S(═O)₂—NH—C₁₋₆-alkyl,—S(═O)₂—NH-phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,pyrrolidinyl, piperidinyl, thiophenyl, phenoxy, —O-Benzyl, and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, phenyl, cyclohexyl, pyrrolidinyl, piperidinyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃;

an unsubstituted or at least mono-substituted C₃₋₁₆ cycloalkyl radicalor C₄₋₁₆ cycloalkenyl radical, which in each case is bonded via anunsubstituted or at least mono-substituted C₁₋₅ alkylene group, C₂₋₅alkenylene group or C₂₋₅ alkinylene group and/or may be condensed withan unsubstituted or at least mono-substituted mono- or polycyclic ringsystem and/or may be bridged by at least one unsubstituted or at leastmono-substituted C₁₋₅ alkylene group;

or an unsubstituted or at least mono-substituted C₄₋₁₆ heterocycloalkylradical or C₅₋₁₆ heterocycloalkenyl radical, which in each case isbonded via an unsubstituted or at least mono-substituted C₁₋₅ alkylenegroup, C₂₋₅ alkenylene group or C₂₋₅ alkinylene group and/or may becondensed with an unsubstituted or at least mono-substituted mono- orpolycyclic ring system and/or may be bridged by at least oneunsubstituted or at least mono-substituted C₁₋₅ alkylene group;

a —NR⁷R⁸ moiety; a —P(═O)(OR⁹)₂ moiety; a —C(═)—OR¹⁰ moiety; a—C(═O)—NH—R¹¹ moiety or a —C(═O)—R¹² moiety;

R⁶ represents an unsubstituted or at least mono-substituted C₅₋₁₆ alkylradical, C₂₋₁₆ alkenyl radical or C₂₋₁₆ alkinyl radical;

an unsubstituted or at least mono-substituted C₃₋₁₆ cycloalkyl radicalor C₄₋₁₆ cycloalkenyl radical, which in each case may be condensed withan unsubstituted or at least mono-substituted mono- or polycyclic ringsystem and/or may be bridged by at least one unsubstituted or at leastmono-substituted C₁₋₅ alkylene group:

an unsubstituted or at least mono-substituted C₄₋₁₆ heterocycloalkylradical or C₅₋₁₆ heterocycloalkenyl radical, which in each case may becondensed with an unsubstituted or at least mono-substituted mono- orpolycyclic ring system and/or may be bridged by at least oneunsubstituted or at least mono-substituted C₁₋₅ alkylene group;

a —P(═O)(OR⁹)₂ moiety; a —C(═O)—OR¹⁰ moiety; a —C(═O)—NH—R¹¹ moiety or a—C(═O)—R¹² moiety;

R⁷ represents a hydrogen atom or an unsubstituted or at leastmono-substituted C₁₋₁₆ alkyl radical, C₂₋₁₆ alkenyl radical or C₂₋₁₆alkinyl radical;

R⁸ represents an unsubstituted or at least mono-substituted radicalselected from the group consisting of 2-pentyl, 3-pentyl, neo-pentyl,2-hexyl, 3-hexyl, 2-heptyl, 3-heptyl, 4-heptyl, 2-octyl, 3-octyl,4-octyl, 2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl, 2-(5-methyl )-hexyl,2-(4-methyl)-hexyl, 2-(7-methyl)-octyl, 2-(6-methyl)-octyl, —O-methyl,—O-ethyl, —O-n-propyl, —O-isopropyl, —O-n-butyl, —O-isobutyl,—O-tert-butyl, —O-n-pentyl and —O-n-hexyl;

a substituted radical selected from the group consisting of methyl,ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl,n-hexyl, n-heptyl and n-octyl, which is substituted with 1, 2, 3, 4, 5,6, 7, 8 or 9 substituents independently selected from the groupconsisting of —NH—C₁₋₆-alkyl, —N(C₁₋₆-alkyl)₂, —C(═O)—O—C₁₋₆-alkyl and—NH—C(═O)—C₁₋₆-alkyl;

an unsubstituted or at least mono-substituted radical selected from thegroup consisting of cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl),(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —C₁₋₆-alkyl substituted withone or more hydroxy groups, —C₁₋₆-alkyl substituted with one or morechlorine atoms, —C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —O—C₁₋₆-alkyl substituted with one or more methoxy and/orethoxy groups, —S—C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, —O—C(═O)—C₁₋₆-alkyl,—SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—C₁₋₆-alkyl,—N(C₁₋₆-alkyl)-C(═O)—C₁₋₆-alkyl, —CHO, —C(═O)—C₁₋₆-perfluoroalkyl,—C(═S)—NH—C₁₋₆-alkyl, —CF₂H, —CFH₂, —C(═O)—NH—NR^(C)R^(D),—S(═O)₂-phenyl, —(C₁₋₆-alkylene)-S—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl,—NR^(A)R^(B), —(C₁₋₅-alkylene)-NR^(A)R^(B), —S(═O)₂—NH—C₁₋₆-alkyl,—S(═O)₂—NH-phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,pyrrolidinyl, piperidinyl, thiophenyl, phenoxy and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, phenyl, pyrrolidinyl, piperidinyl, thiophenyl,phenoxy and benzyl can optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of F,Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and—S—CF₃; an unsubstituted or at least mono-substituted C₃₋₁₆ cycloalkylradical or C₄₋₁₆ cycloalkenyl radical, which in each case is bonded viaan unsubstituted or at least mono-substituted C₁₋₅ alkylene group, C₂₋₅alkenylene group or C₂₋₅ alkinylene group and/or may be condensed withan unsubstituted or at least mono-substituted mono- or polycyclic ringsystem and/or may be bridged by at least one unsubstituted or at leastmono-substituted C₁₋₅ alkylene group;

or an unsubstituted or at least mono-substituted C₄₋₁₅ heterocycloalkylradical or C₅₋₁₆ heterocycloalkenyl radical, which in each case isbonded via an unsubstituted or at least mono-substituted C₁₋₅ alkylenegroup C₂₋₅ alkenylene group or C₂₋₅ alkinylene group and/or

may be condensed with an unsubstituted or at least mono-substitutedmono- or polycyclic ring system and/or may be bridged by at least oneunsubstituted or at least mono-substituted C₁₋₅ alkylene group;

R⁹, R¹⁰, R¹¹ and R¹², independently of one another, in each caserepresent an optionally at least mono-substituted C₅₋₁₆ alkyl radical,C₂₋₁₆ alkenyl radical or C₂₋₁₆ alkinyl radical;

an unsubstituted or at least mono-substituted 6- or 10-membered arylradical, which may be condensed with an unsubstituted or at leastmono-substituted mono- or polycyclic ring system and/or may be bondedvia an unsubstituted or at least mono-substituted C₁₋₅ alkylene group,C₂₋₅ alkenylene group or C₂₋₅ alkinylene group;

an unsubstituted or at least mono-substituted 5- to 14-memberedheteroaryl radical, which may be condensed with an unsubstituted or atleast mono-substituted mono- or polycyclic ring system and/or may bebonded via an unsubstituted or at least mono-substituted C₁₋₅ alkylenegroup, C₂₋₅ alkenylene group or C₂₋₅ alkinylene group;

R^(A) and R^(B), independently of one another, in each case representhydrogen or —C₁₋₆-alkyl or R^(A) and R^(B) in each case together withthe bridging nitrogen atom form a radical selected from the groupconsisting of pyrrolidinyl, imidazolidinyl, piperazinyl, piperidinyl,thiomorpholinyl, morpholinyl, azepanyl and diazepanyl which may be atleast mono-substituted with one or more identical or different C₁₋₆alkyl radicals; and

R^(C) and R^(D), independently of one another, in each case representhydrogen, —C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl, C₃₋₈-cycloalkyl,—(C₁₋₅-alkylene)-C₃₋₈-cycloalkyl, —(C₁₋₆-alkylene)-O—C₁₋₆-alkyl or—C₁₋₆-alkyl substituted with one or more hydroxy groups or R^(C) andR^(D) in each case together with the bridging nitrogen atom form aradical selected from the group consisting of pyrrolidinyl,imidazolidinyl, piperazinyl, piperidinyl, thiomorpholinyl, morpholinyl,azepanyl and diazepanyl which may be at least mono-substituted with oneor more substituents independently selected from the group consisting—C₁₋₆-alkyl, —C(═O)-C₁₋₆-alkyl, —C(═O)—O—C₁₋₆-alkyl,—C(═O)—NH—C₁₋₆-alkyl, —C(═S)—NH—C₁₋₆-alkyl, oxo (═O), —C₁₋₆-alkylsubstituted with one or more hydroxy groups,—(C₁₋₆-alkylene)-O—C₁₋₆-alkyl and —C(═O)—NH₂;

whereby

the rings of the aforementioned ring system are in each caseindependently of one another 5- 6- or 7-membered and may in each caseindependently of one another optionally contain 1, 2 or 3 heteroatom(s)independently selected from the group consisting of nitrogen, oxygen andsulfur;

the aforementioned heteroaryl radicals in each case optionally contain1, 2, 3 or 4 heteroatom(s) independently selected from the groupconsisting of nitrogen, oxygen and sulfur as ring member(s);

the aforementioned heterocycloalkyl radicals and heterocycloalkenylradicals in each case optionally contain 1, 2, 3 or 4 heteroatom(s)independently selected from the group consisting of nitrogen, oxygen andsulfur as ring member(s);

optionally in form of one of its stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofits stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding N-oxide thereof, or a physiologicallyacceptable salt thereof, or a corresponding solvate thereof.

Preferred are substituted pyrazoline compounds of general formula Igiven above, wherein R¹ and R², independently of one another, in eachcase represent a phenyl radical which may be substituted with 1, 2, 3, 4or 5 substituent(s) independently selected from the group consisting of—CF₃, —C₂F₅, —C₃F₇, —C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃,—O—C(CH₃)₃, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅,—O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, F, Cl, Br, I,—CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —NO₂; —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —C(═S)—NH—CH₃, —(═S)—NH—C₂H₅, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂,—C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—N₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby in each case the cyclic moieties cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl,thiophenyl, phenoxy and benzyl may optionally be substituted with 1, 2or 3 substituent(s) independently selected from the group consisting ofF, Cl, Br, methyl, ethyl and n-propyl;

and R³ to R¹² and R^(A), R^(B), R^(C) and R^(D) have the meaning givenabove, optionally in form of one of the stereoisomers, preferablyenantiomers or diastereomers, a racemate or in form of a mixture of atleast two of the stereoisomers, preferably enantiomers and/ordiastereomers, in any mixing ratio, or a corresponding N-oxide thereof,or a corresponding salt thereof, or a corresponding solvate thereof.

Preference is also given to substituted pyrazoline compounds of generalformula I given above, wherein R³ represents a radical selected from thegroup consisting of cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2,2,1]heptyl, bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl, 8-aza-spiro[4.5]decanyland (2,3)-dihydro-1H-cyclopenta[b]-indolyl, which may optionally besubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of oxo (═O), thioxo (═S), —CF₃, —C₂F₅, —C₃F₇,—C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl, 2-pentyl, n-hexyl,—CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃,—O—CH₂—CH₂CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃,—O—C(CH₃)₃, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅,—O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, F, Cl, Br, I,—CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═)—C(CH₃)₃, —NO₂, —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂,—C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby in each case the cyclic moieties cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl,thiophenyl, phenoxy and benzyl may optionally be substituted with 1, 2or 3 substituent(s) independently selected from the group consisting ofF, Cl, Br, methyl, ethyl and n-propyl;

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —CH₂—OH, —CH₂—CH₂—OH,—CH₂—CH₂—CH₂—OH, —CH₂Cl, —CHCl₂, —C₂H₄Cl, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—S—CH₃, —S—C₂H₅, —CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃,—S—C(CH₃)₃, C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂,—O—C(═O)—CH₂—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, —SCF₃, —SCF₂H, —SCFH₂, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —CHO,—C(═O)—CF₃, —C(═O)—C₂F₅, —C(═O)—C₃F₇, —CF₂H, —CFH₂, —C(═O)—NH—NH—CH₃,—C(═O)—NH—NH—C₂H₅; —C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)₂-phenyl,—(C₁₋₅-alkylene)-S—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl, —N(CH₃)₂, —N(C₃H₅)₂, —CH₂—N(CH₃)₂,—(CH₂)-morpholinyl, —(CH₂)-piperidinyl, —(CH₂)-piperazinyl,—(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂, —CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅),cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl,piperidinyl, thiophenyl, phenoxy and benzyl; whereby in each case thecyclic moieties cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,phenyl, pyrrolidinyl, piperidinyl, thiophenyl, phenoxy and benzyl canoptionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of F, Cl, Br, I, —OH,—CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and —S—CF₃;

a —NR⁴R⁵ moiety

or a —O—R⁶ moiety;

and R¹, R², R⁴ to R¹² and R^(A), R^(B), R^(C) and R^(D) have the meaninggiven above, optionally in form of one of the stereoisomers, preferablyenantiomers or diastereomers, a racemate or in form of a mixture of atleast two of the stereoisomers, preferably enantiomers and/ordiastereomers, in any mixing ratio, or a corresponding N-oxide thereof,or a corresponding salt thereof, or a corresponding solvate thereof,

Preferred are substituted pyrazoline compounds of general formula Igiven above, wherein R⁴ represents a hydrogen atom or a radical selectedfrom the group consisting of methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl,neo-pentyl, n-hexyl, 2-hexyl, 3-hexyl, n-heptyl, 2-heptyl, 3-heptyl,4-heptyl, n-octyl, 2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl,2-(5-methyl)-heptyl, 2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl,2-(7-methyl)-octyl, 2-(6-methyl)-octyl, n-nonyl, n-decyl, n-undecyl,n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecycl, n-hexadecyl, —CF₃,—CH₂F, —CF₂H, —CH₂—O—CH₃, —C₂F₅, —CH₂—CH₂—F, —CH₂—CN, —CH₂—OH,—CH₂—CH₂—CN, —CH₂—CH₂—OH, —CH₂—CH₂—OCH₃, —CH₂—CH₂—CH₂—CN,—CH₂—CH₂—CH₂—OH, —CH₂—CH₂—CH₂—O—CH₃, —CH₂—CH₂—CH₂—CH₂—O—CH₃, —CH₂—NH₂,—CH₂—N(CH₃)₂, —CH₂—CH—NH₂, —CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂,—CH₂—CH₂—CH₂—NH₂, —CH₂—CH₂—CH₂—N(CH₃)₂ and —CH₂—CH₂—CH₂—N(C₂H₅)₂;

and R¹ to R³, R⁵ to R¹² and R^(A), R^(B), R^(C) and R^(D) have themeaning given above, optionally in form of one of the stereoisomers,preferably enantiomers or diastereomers, a racemate or in form of amixture of at least two of the stereoisomers, preferably enantiomersand/or diastereomers, in any mixing ratio, or a corresponding N-oxidethereof, or a corresponding salt thereof, or a corresponding solvatethereof,

Preferred are substituted pyrazoline compounds of general formula Igiven above, wherein R⁵ represents a radical selected from the groupconsisting of 2-pentyl, 3-pentyl, neo-pentyl, 2-hexyl, 3-hexyl,2-heptyl, 3-heptyl, 4-heptyl, 2-octyl, 3-octyl, 4-octyl,2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl, 2-(5-methyl)-hexyl,2-(4-methyl)-hexyl, 2-(7-methyl )-octyl, 2-(6-methyl)-octyl, —O-methyl,—O-ethyl, —O-n-propyl, —O-isopropyl, —O-n-butyl, —O-isobutyl,—O-tert-butyl, —O-n-pentyl, —O-n-hexyl, —CH₂—N(CH₃)₂, —CH₂—N(C₂H₅)₂,—CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂N(C₂H₅)₂, —CH₂—CH₂—CH₂—N(CH₃)₂ and—CH₂—CH₂—CH₂—N(C₂H₅)₂;

a radical selected from the group consisting of adamantyl, cyclononyl,cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl,aziridinyl, azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl,tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2.3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,which may optionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of oxo (═O), thioxo(═S), —CF₃, —C₂F₅, —C₃F₇, —C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃,—O—C(CH₃)₃, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃, —O—C(═)—CH₃,—O—C(═O)—C₂H₅,—O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, F, Cl, Br, I,—CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —NO₂, —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂,—C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃, —NH—CH₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₃H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby in each case the cyclic moieties cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl,thiophenyl, phenoxy and benzyl may optionally be substituted with 1, 2or 3 substituent(s) independently selected from the group consisting ofF, Cl, Br, methyl, ethyl and n-propyl;

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —CH₂—OH, —CH₂—CH₂—OH,—CH₂—CH₂—CH₂—OH, —CH₂Cl, —CHCl₂, —C₂H₄Cl, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃,—S—C(CH₃)₃, C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃,—O—C(═O)—C(CH₃)₃, —SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—CH₃,—NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —CHO, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —CF₂H, —CFH₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅,—C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)₂-phenyl,—(C₁₋₅-alkylene)-S—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl,—(C₁₋₆-alkylene)-S(═O)₂—C₁₋₆-alkyl, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂,—(CH₂)-morpholinyl, —(CH₂)-piperidinyl, —(CH₂)-piperazinyl,—(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂, —CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅),cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl,piperidinyl, thiophenyl, phenoxy, —O-Benzyl, and benzyl: whereby in eachcase the cyclic moieties cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, phenyl, pyrrolidinyl, piperidinyl, thiophenyl, phenoxy andbenzyl can optionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of F, Cl, Br, I, —OH,—CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and —S—CF₃;

a radical selected from the group consisting of(1,2,3,4)-tetrahydronaphthyl, (2,3)-dihydro-1H-cyclopenta[b]indolyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, pyrrolidinyl, piperidinyl, piperazinyl,homopiperazinyl, morpholinyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl and norbornenyl, which is bonded via a —(CH₂)—,—(CH₂)—(CH₂)—, —(CH₂)—(CH₂)—(CH₂)— or —CH═CH-group and/or may optionallybe substituted with 1, 2, 3, 4 or 5 substituent(s) independentlyselected from the group consisting of oxo (═O), thioxo (═S), —CF₃,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl,tert-butyl, n-pentyl, 2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃,—O—CH₂—O—CH₃, —O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂,—C(OCH₃)(CH₃)₂, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, F, Cl, Br, I, —CN, —OCF₃, —SCF₃, —SCF₂H,—SCFH₂, —OH, —SH, —NO₂, —CHO, —C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C(CH₃)₃, —CF₂H, —CFH₂,—C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇,—S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, N(C₂H₅)₂, cyclopentyl, cyclohexyl, pyrrolidinyl andpiperidinyl;

a —NR⁷R⁸ moiety; a —P(═O)(OR⁹)₂ moiety; a —C(═O)—OR¹⁰ moiety: a—C(═O)—NH—R¹¹ moiety or a —C(═O)—R¹² moiety;

and R¹ to R⁴, R⁶ to R¹² and R^(A), R^(B), R^(C) and R^(D) have themeaning given above, optionally in form of one of the stereoisomers,preferably enantiomers or diastereomers, a racemate or in form of amixture of at least two of the stereoisomers, preferably enantiomersand/or diastereomers, in any mixing ratio, or a corresponding N-oxidethereof, or a corresponding salt thereof, or a corresponding solvatethereof.

Preference is also given to substituted pyrazoline compounds of generalformula I given above, wherein R⁶ represents a radical selected from thegroup consisting of n-pentyl, 2-pentyl, 3-pentyl, neo-pentyl, n-hexyl,2-hexyl, 3-hexyl, n-heptyl, 2-heptyl, 3-heptyl, 4-heptyl, n-octyl,2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl,2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl, 2-(7-methyl)-octyl,2-(6-methyl)-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl,n-tetradecyl, n-pentadecycl and n-hexadecyl;

a radical selected from the group consisting of(1,2,3,4)-tetrahydronaphthyl, (2,3)-dihydro-1H-cyclopenta[b]indolyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, pyrrolidinyl, piperidinyl, piperazinyl,homopiperazinyl, morpholinyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4-H-pyrimidinyl,oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1 ]heptyl and norbornenyl, which may optionally besubstituted with 1, 2, 3.4 or 5 substituent(s) independently selectedfrom the group consisting of oxo (═O), thioxo (═S), —CF₃, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂,—O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —O—CH₂—O—CH₃, —O—CH₂—CH₂—O—CH₃,—O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂, —S—CH₃, —S—C₂H₅,—S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, F, Cl, Br,I, —CN, —OCF₃, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —NO₂, —CHO, —C(═O)—CH₃,—C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—C(CH₃)₃, —CF₂H, —CFH₂, —C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅,—C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —S(═O)—CH₃,—S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —NH₂,—NH—CH₃, —NH—C₂H₅, —N(CH₃)₂, —N(C₂H₅)₂, cyclopentyl, cyclohexyl,pyrrolidinyl and piperidinyl;

a —P(═O)(OR⁹)₂ moiety: a —C(═O)—OR¹⁰ moiety; a —C(═O)—NH—R¹¹ moiety or a—C(═O—R¹² moiety;

and R¹ to R⁵, R⁷ to R¹² and R^(A), R^(B), R^(C) and R^(D) have themeaning given above, optionally in form of one of the stereoisomers,preferably enantiomers or diastereomers, a racemate or in form of amixture of at least two of the stereoisomers, preferably enantiomersand/or diastereomers, in any mixing ratio, or a corresponding N-oxidethereof, or a corresponding salt thereof, or a corresponding solvatethereof.

Preferred are substituted pyrazoline compounds of general formula Igiven above, wherein R⁷ represents a hydrogen atom or a radical selectedfrom the group consisting of methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl,neo-pentyl, n-hexyl, 2-hexyl, 3-hexyl, n-heptyl, 2-heptyl, 3-heptyl,4-heptyl, n-octyl, 2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl,2-(5-methyl)-heptyl, 2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl,2-(7-methyl)-octyl, 2-(6-methyl)-octyl, n-nonyl, n-decyl, n-undecyl,n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecycl, n-hexadecyl, —CF₃,—CH₂F, —CF₂H, —CH₂—O—OH₃, —C₂F₅, —CH₂—CH₂F, —CH₂—CN, —CH₂—OH,—CH₂—CH₂—CN, —CH₂—CH₂—OH, —CH₂—CH₂—OCH₃, —CH₂—CH₂—CH₂—CN,—CH₂—CH₂—CH₂—OH, —CH₂—CH₂—CH₂—O—CH₃, —CH₂—CH₂—CH₂—CH₂—O—CH₃, —CH₂—NH₂,—CH₂—N(CH₃)₂, —CH₂—CH—NH₂, —CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂,—CH₂—CH₂—CH₂—NH₂, —CH₂—CH₂—CH₂—N(CH₃)₂ and —CH₂—CH₂—CH₂—N(C₂H₅)₂;

and R¹ to R⁶, R⁸ to R¹² and R^(A), R^(B), R^(C) and R^(D) have themeaning given above, optionally in form of one of the stereoisomers,preferably enantiomers or diastereomers, a racemate or in form of amixture of at least two of the stereoisomers, preferably enantiomersand/or diastereomers, in any mixing ratio, or a corresponding N-oxidethereof, or a corresponding salt thereof, or a corresponding solvatethereof.

Preference is also given substituted pyrazoline compounds of generalformula I given above, wherein R⁸ represents a radical selected from thegroup consisting of 2-pentyl, 3-pentyl, neo-pentyl, 2-hexyl, 3-hexyl,2-heptyl, 3-heptyl, 4-heptyl, 2-octyl, 3-octyl, 4-octyl,2-(6-methyl)-heptyl, 2-(5-methyl)heptyl, 2-(5-methyl)-hexyl,2-(4-methyl)-hexyl, 2-(7-methyl)-octyl, 2-(6-methyl)-octyl, —O-methyl,—O-ethyl, —O-n-propyl, —O-isopropyl, —O-n-butyl, —O-isobutyl,—O-tert-butyl, —O-n-pentyl, —O-n-hexyl, —CH₂—N(CH₃)₂, —CH₂—N(C₂H₅)₂,—CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂, —CH₂—CH₂—CH₂—N(CH₃)₂ and—CH₂—CH₂—CH₂—N(C₂H₅)₂;

a radical selected from the group consisting of cyclononyl, cyclodecyl,cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl, aziridinyl,azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl,tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,which may optionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of oxo (═O), thioxo(═S), —CF₃, —C₂F₅, —C₃F₇, —C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃,—CH₂—O—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃,—O—C(CH₃)₃, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O )—O—C₃H₇, —C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅,—O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃,—O—C(═O)—C(CH₃)₃, F, Cl, Br, I, —CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉,—SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅,—NH—C(═O)—C(CH₃)₃, —NO₂, —CHO, —C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃,—C(═O)—CF₃, —C(═O)—C₂F₅, —C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅,—CF₂H, —CFH₂, —C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅,—C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇,—S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃,—NH—C₂H₅, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby in each case the cyclic moieties cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl,thiophenyl, phenoxy and benzyl may optionally be substituted with 1, 2or 3 substituent(s) independently selected from the group consisting ofF, Cl, Br, methyl, ethyl and n-propyl;

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —CH₂—OH, —CH₂—CH₂—OH,—CH₂—CH₂—CH₂—OH, —CH₂Cl, —CHCl₂, —C₂H₄Cl, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃,—S—C(CH₃)₃, C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃,—O—C(═O)—C(CH₃)₃, —SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—CH₃,—NH—C(C═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —CHO, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —CF₂H, —CFH₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅,—C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)₂-phenyl,—(C₁₋₅-alkylene)-S—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂,—(CH₂)-morpholinyl, —(CH₂)-piperidinyl, —(CH₂)-piperazinyl,—(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂, —CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅),cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl,piperidinyl, thiophenyl, phenoxy and benzyl; whereby in each case thecyclic moieties cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,phenyl, pyrrolidinyl, piperidinyl, thiophenyl, phenoxy and benzyl canoptionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of F, Cl, Br, I, —OH,—CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and —S—CF₃;

or a radical selected from the group consisting of(1,2,3,4)-tetrahydronaphthyl, (2,3)-dihydro-1H-cyclopenta[b]indolyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, pyrrolidinyl, piperidinyl, piperazinyl,homopiperazinyl, morpholinyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl and norbornenyl, which is bonded via a —(CH₂)—,—(CH₂)—(CH₂)—, —(CH₂)—(CH₂)—(CH₂)— or —CH═CH-group and/or may optionallybe substituted with 1, 2, 3, 4 or 5 substituent(s) independentlyselected from the group consisting of oxo (═O), thioxo (═S), —CF₃,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl,tert-butyl, n-pentyl, 2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅H,—O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃,—O—CH₂—O—CH₃, —O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂,—C(OCH₃)(CH₃)₂, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, F, Cl, Br, I, —CN, —OCF₃, —SCF₃, —SCF₂H,—SCFH₂, —OH, —SH, —NO₂, —CHO, —C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C(CH₃)₃, —CF₂H, —CFH₂,—C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇,—S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, cyclopentyl, cyclohexyl, pyrrolidinyl andpiperidinyl;

and R¹ to R₇, R⁹ to R¹² and R^(A), R^(B), R^(C) and R^(D) have themeaning given above, optionally in form of one of the stereoisomers,preferably enantiomers or diastereomers, a racemate or in form of amixture of at least two of the stereoisomers, preferably enantiomersand/or diastereomers, in any mixing ratio, or a corresponding N-oxidethereof, or a corresponding salt thereof, or a corresponding solvatethereof.

Preferred are substituted pyrazoline compounds of general formula Igiven above, wherein R⁹, R¹⁰, R¹¹ and R¹², independently of one another,in each case represent a radical selected from the group consisting ofmethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, neo-pentyl, n-hexyl, 2-hexyl,3-hexyl, n-heptyl, 2-heptyl, 3-heptyl, 4-heptyl n-octyl, 2-octyl,3-octyl, 4-octyl, vinyl, n-propenyl, n-butenyl, n-pentenyl, n-hexenyl,ethinyl, propinyl, n-butinyl, n-pentinyl and n-hexinyl, which mayoptionally be substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9substituent(s) independently selected from the group consisting of NH₂,—NH—CH₃, —NH—C₂H₅, —N(CH₃)₂, —N(C₂H₅)₂, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅,—NH—C(═O)—C(CH₃)₃, —NH—C(═O)—O—CH₃, —NH—C(═O)—O—C₂H₅,—NH—C(═O)—O—C(CH₃)₃, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C(CH₃)₃,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —OH, —C(═O)—OH, —C(═O)—O—CH₃,—C(═O)—O—C₂H₅, —C(═O)—O—C(CH₃)₃, —C(═O)—CH₃, —C(═O)—C₂H₅ and—C(═O)—C(CH₃)₃;

or a radical selected from the group consisting of phenyl, naphthyl,pyridinyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl,thiadiazolyl, triazolyl, pyridazinyl, indolyl and isoindolyl, which maybe bonded via a —(CH₂)—, —(CH₂)—(CH₂)—, —(CH₂)—(CH₂)—(CH₂)— or—CH═CH-group and/or may optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of —CF₃,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl,tert-butyl, n-pentyl, 2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —S—CH₃,—S—C₂H₅, —S—CH₂CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, F,Cl, Br, I, —CN, —OCF₃, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —NO₂, —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —NH₂, —NH—CH₃, —NH—C₂H₅, —N(CH₃)₂,—N(C₂H₅)₂, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂,—O—C(═O)—CH₂—CH₂—CH₃, —CH₂—N(CH₃)₂, —(CH₂)—N(CH₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅) and —(CH₂)-morpholinyl;

and R¹ to R⁸ and R^(A), R^(B), R^(C) and R^(D) have the meaning givenabove, optionally in form of one of the stereoisomers, preferablyenantiomers or diastereomers, a racemate or in form of a mixture of atleast two of the stereoisomers, preferably enantiomers and/ordiastereomers, in any mixing ratio, or a corresponding N-oxide thereof,or a corresponding salt thereof, or a corresponding solvate thereof.

Preference is also given to substituted pyrazoline compounds of generalformula I given above, wherein R^(A) and R^(B), independently of oneanother, in each case represent hydrogen or methyl, ethyl, n-propyl,isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl or R^(A) andR^(B) in each case together with the bridging nitrogen atom form aradical selected from the group consisting of pyrrolidinyl,imidazolidinyl, piperazinyl, piperidinyl, thiomorpholinyl, morpholinyl,azepanyl and diazepanyl; and

R^(C) and R^(D), independently of one another, in each case representhydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl,isobutyl, tert-butyl, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)O—C(CH₃)₃,cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl or R^(C) and R^(D) ineach case together with the bridging nitrogen atom form a radicalselected from the group consisting of pyrrolidinyl, imidazolidinyl,piperazinyl, piperidinyl, thiomorpholinyl, morpholinyl, azepanyl anddiazepanyl;

and R¹ to R¹² have the meaning given above, optionally in form of one ofthe stereoisomers, preferably enantiomers or diastereomers, a racemateor in form of a mixture of at least two of the stereoisomers, preferablyenantiomers and/or diastereomers, in any mixing ratio, or acorresponding N-oxide thereof, or a corresponding salt thereof, or acorresponding solvate thereof.

Preferred are substituted pyrazoline compounds of general formula Igiven above, wherein

R¹ and R², independently of one another, in each case represent a phenylradical which may be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of —CF₃, —C₂F₅, —C₃F₇,—C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl, 2-pentyl, n-hexyl,—CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃, —O—CH₂—CH₂—O—CH₃,—O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —S—CH₃,—S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃,—O—CO(═O)—C(CH₃)₃, F, Cl, Br, I, —CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉,—SCF₃, —SCF₂H, —SCFH₂, —OH, —SH —SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅,—NH—C(═O)—C(CH₃)₃, —NO₂, —CHO, —C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃,—C(═O)—CF₃, —C(═O)—C₂F₅, —C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅,—CF₂H, —CFH₂, —C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅,—C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇,—S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃,—NH—C₂H₅, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby in each case the cyclic moieties cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl,thiophenyl, phenoxy and benzyl may optionally be substituted with 1, 2or 3 substituent(s) independently selected from the group consisting ofF, Cl, Br, methyl, ethyl and n-propyl.

R³ represents a radical selected from the group consisting ofcyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl,cyclotetradecyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,which may optionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of oxo (═O), thioxo(═S), —CF₃, —C₂F₅, —C₃F₇, —C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃,—O—C(CH₃)₃, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅,—O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, F, Cl, Br, I,—CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —NO₂, —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂,—C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby in each case the cyclic moieties cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl,thiophenyl, phenoxy and benzyl may optionally be substituted with 1, 2or 3 substituent(s) independently selected from the group consisting ofF, Cl, Br, methyl, ethyl and n-propyl;

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —CH₂—OH, —CH₂—CH₂—OH,—CH₂—CH₂—CH₂—OH, —CH₂Cl, —CHCl₂, —C₂H₄Cl, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃,—S—C(CH₃)₃, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇,—C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂,—O—C(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, —SCF₃, —SCF₂H, —SCFH₂, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —CHO,—C(═O)—CF₃, —C(═O)—C₂F₅, —C(═O)—C₃F₇, —CF₂H, —CFH₂, —C(═O)—NH—NH—CH₃,—C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)₂-phenyl,—(C₁₋₅-alkylene)-S—C₁₋₆-alkyl, —(C₁₋₆-alkylene)-S(═O)—C₁₋₆-alkyl,—(C₁₋₅-alkylene)—S(═O)₂—C₁₋₆-alkyl, —N(CH₃)₂, N(C₂H₅)₂, —CH₂—N(CH₂)₂,—(CH₂)-morpholinyl, —(CH₂)-piperidinyl, —(CH₂)-piperazinyl,—(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂, —CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅),cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl,piperidinyl, thiophenyl, phenoxy and benzyl; whereby in each case thecyclic moieties cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,phenyl, pyrrolidinyl, piperidinyl, thiophenyl, phenoxy and benzyl canoptionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of F, Cl, Br, I, —OH,—CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—C₁₋₆-alkyl, —O—CF₃ and —S—CF₃;

a —NR⁴R⁵ moiety

or a —O—R⁶ moiety;

R⁴ represents a hydrogen atom or a radical selected from the groupconsisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, neo-pentyl,n-hexyl, 2-hexyl, 3-hexyl, n-heptyl, 2-heptyl, 3-heptyl, 4-heptyl,n-octyl, 2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl,2-(5-methyl)heptyl, 2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl,2-(7-methyl)-octyl, 2-(6-methyl)-octyl, n-nonyl, n-decyl, n-undecyl,n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecycl, n-hexadecyl, —CF₃,—CH₂F, —CF₂H, —CH₂—O—CH₃, —C₂F₅, —CH₂—O—H₂—F, —CH₂—CN, —CH₂—OH,—CH₂—CH₂—CN, —CH₂—CH₂—OH, —CH₂—CH₂—OCH₃, —CH₂—CH₂—CH₂—CN,—CH₂—CH₂—CH₂—OH, —CH₂—CH₂—CH₂—O—CH₃, —CH₂—CH₂—CH₂—CH₂—O—CH₃, —CH₂—NH₂,—CH₂—N(CH₃)₂, —CH₂—CH—NH₂, —CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂,—CH₂CH₂—CH₂—NH₂, —CH₂—CH₂—CH₂—N(CH₃)₂ and —CH₂—CH₂—CH₂—N(C₂H₅)₂;

R⁵ represents a radical selected from the group consisting of 2-pentyl,3-pentyl, neo-pentyl, 2-hexyl, 3-hexyl, 2-heptyl, 3-heptyl, 4-heptyl,2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl,2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl, 2-(7-methyl)-octyl,2-(6-methyl)-octyl, —O-methyl, —O-ethyl, —O-n-propyl, —O-isopropyl,—O-n-butyl, —O-isobutyl, —O-tert-butyl, —O-n-pentyl, —O-n-hexyl,—CH₂—N(CH₃)₂, —CH₂—N(C₂H₅)₂, —CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂,—CH₂—CH₂—CH₂—N(CH₃)₂ and —CH₂—CH₂—CH₂—N(C₂H₅)₂;

a radical selected from the group consisting of adamantyl, cyclononyl,cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl,aziridinyl, azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl,tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4 )-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]indolyl, whichmay optionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of oxo (═O), thioxo(═S), —CF₃, —C₂F₅, —C₃F₇, —C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₄Cl, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃,—O—C(CH₃)₃, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅,—O—C(═O)—CH(CH₃)₂, —O—(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, F, Cl, Br, I,—CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —NO₂, —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂,—C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₂H₅, —S(═O)₂-phenyl, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby in each case the cyclic moieties cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl,thiophenyl, phenoxy and benzyl may optionally be substituted with 1, 2or 3 substituent(s) independently selected from the group consisting ofF, Cl, Br, methyl, ethyl and n-propyl;

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —CH₂—OH, —CH₂—CH₂—OH,—CH₂—CH₂—CH₂—OH, —CH₂Cl, —CHCl₂, —C₂H₄Cl, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃,—S—C(CH₃)₃, C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃,—O—C(═O)—C(CH₃)₃, —SCF₃, —SCF₂H, —SCFH₂, —SH, —SO₃H, —NH—C(═O)—CH₃,—NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —CHO, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —CF₂H, —CFH₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅,—C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)₂-phenyl,—(C₁₋₅-alkylene)-S—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl,—(C₁₋₆-alkylene)-S(═O)₂—C₁₋₆-alkyl, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂,—(CH₂)-morpholinyl, —(CH₂)-piperidinyl, —(CH₂)-piperazinyl,—(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂, —CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅),cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl,piperidinyl, thiophenyl, phenoxy and benzyl;

whereby in each case the cyclic moieties cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, phenyl, pyrrolidinyl, piperidinyl, thiophenyl,phenoxy, —O-Benzyl and benzyl can optionally be substituted with 1, 2,3, 4 or 5 substituent(s) independently selected from the groupconsisting of F, Cl, Br, I, —OH, —CF₃, —CN, —NO₂, —C₁₋₆-alkyl,—O—C₁₋₆-alkyl, —O—CF₃ and —S—CF₃;

a radical selected from the group consisting of(1,2,3,4)-tetrahydronaphthyl, (2,3)-dihydro-1H-cyclopenta[b]indolyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, pyrrolidinyl, piperidinyl, piperazinyl,homopiperazinyl, morpholinyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)0dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl and norbornenyl, which is bonded via a —(CH₂)—,—(CH₂)—(CH₂)—, —(CH₂)—(CH₂)—(CH₂)— or —CH═CH-group and/or may optionallybe substituted with 1, 2, 3, 4 or 5 substituent(s) independentlyselected from the group consisting of oxo (═C), thioxo (═S), —CF₃,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl,tert-butyl, n-pentyl, 2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—CH(₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂CH₃,—S—C(CH₃)₂, F, Cl, Br, I, —CN, —OCF₃, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH,—NO₂, —CHO, —C(═O)—CH₃, —C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C(CH₃)₃, —CF₂H, —CFH₂,—C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃—H₇,—C(═C)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇,—S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, cyclopentyl, cyclohexyl, pyrrolidinyl andpiperidinyl;

a —NR⁷R⁸ moiety; a —P(═O)(OR⁹)₂ moiety; a —C(═O)—OR¹⁰ moiety; a—C(═O)—NH—R¹¹ moiety or a —C(═O)—R¹² moiety;

R⁶ represents a radical selected from the group consisting of n-pentyl,2-pentyl, 3-pentyl, neo-pentyl, n-hexyl, 2-hexyl, 3-hexyl, n-heptyl,2-heptyl, 3-heptyl, 4-heptyl, n-octyl, 2-octyl, 3-octyl, 4-octyl,2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl, 2-(5-methyl)-hexyl,2-(4-methyl)-hexyl, 2-(7-methyl)-octyl, 2-(6-methyl)octyl, n-nonyl,n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecycland n-hexadecyl;

a radical selected from the group consisting of(1,2,3,4)-tetrahydronaphthyl, (2,3)-dihydro-1H-cyclopenta[b]indolyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, pyrrolidinyl, piperidinyl, piperazinyl,homopiperazinyl, morpholinyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl and norbornenyl, which may optionally besubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of oxo (═O), thioxo (═S), —CF₃, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂,—O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —O—CH₂—O—CH₃, —O—CH₂—CH₂—O—CH₃,—O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂, —S—CH₃, —S—C₂H₅,—S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, F, Cl, Br,I, —CN, —OCF₃, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —NO₂, —CHO, —C(═O)—CH₃,—C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C(CH₃)₃, —CF₂H, —CFH₂, —C(═O)—NH₂, —C(═O)—NH—CH₃,—C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂,—S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃, —S(═O)₂—C₂H₅,—S(═O)₂—C₃H₇, —NH₂, —NH—CH₃, —NH—C₂H₅, —N(CH₃)₂, —N(C₂H₅)₂, cyclopentyl,cyclohexyl, pyrrolidinyl and piperidinyl;

a —P(═O)(OR⁹)₂ moiety; a —C(═O)—OR¹⁰ moiety; a —C(═O)—NH—R¹¹ moiety or a—C(═O)—R¹² moiety;

R⁷ represents a hydrogen atom or a radical selected from the groupconsisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, neo-pentyl,n-hexyl, 2-hexyl, 3-hexyl, n-heptyl, 2-heptyl, 3-heptyl, 4-heptyl,n-octyl, 2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl,2-(5-methyl)-heptyl, 2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl,2-(7-methyl)-octyl, 2-(6-methyl)-octyl, n-nonyl, n-decyl, n-undecyl,n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecycl, n-hexadecyl, —CF₃,—CH₂F, —CF₂H, —CH₂—O—CH₃, —C₂F₅, —CH₂—CH₂—F, —CH₂—CN, —CH₂—OH,—CH₂—CH₂—CN, —CH₂—CH₂—OH, —CH₂—CH₂—OCH₃, —CH₂—CH₂—CH₂—CN,—CH₂—CH₂—CH₂—OH, —CH₂—CH₂—CH₂—O—CH₃, —CH₂—CH₂—CH₂—CH₂—O—CH₃, —CH₂—NH₂,—CH₂—N(CH₃)₂, —CH₂—CH—NH₂, —CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂,—CH₂—CH₂—CH₂—NH₂, —CH₂—CH₂—CH₂—N(CH₃)₂ and —CH₂—CH₂—CH₂—N(C₂H₅)₂;

R⁸ represents a radical selected from the group consisting of 2-pentyl,3-pentyl, neo-pentyl, 2-hexyl, 3-hexyl, 2-heptyl, 3-heptyl, 4-heptyl,2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl,2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl, 2-(7-methyl)-octyl,2-(6-methyl)-octyl, —O-methyl, —O-ethyl, —O-n-propyl, —O-isopropyl,—O-n-butyl, —O-isobutyl, —O-tert-butyl, —O-n-pentyl, —O-n-hexyl,—CH₂—N(CH₃)₂,—CH₂—N(C₂H₅)₂, —CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂,—CH₂—CH₂—CH₂—N(CH₃)₂ and —CH₂—CH₂—CH₂—N(C₂H₅)₂; a radical selected fromthe group consisting of cyclononyl, cyclodecyl, cycloundecyl,cyclododecyl, cyclotridecyl, cyclotetradecyl, aziridinyl, azetidinyl,imidazolidinyl, thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl,tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, norbornenyl, 8-aza-bicyclo[3.2.1]octyl,8-aza-spiro[4.5]decanyl and (2,3)-dihydro-1H-cyclopenta[b]-indolyl,which may optionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of oxo (═O), thioxo(═S), —CF₃, —C₂F₅, —C₃F₇, —C₄F₉, —CH₂Cl, —CHCl₂, —C₂H₂Cl, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃,—O—C(CH₃)₃, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅,—O—C(═O)—CH(CH₃)₂, —O—C(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, F, Cl, Br, I,—CN, —OCF₃, —O—C₂F₅, —O—C₃F₇, —O—C₄F₉, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —NO₂, —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —C(═O)—CF₃, —C(═O)—C₂F₅,—C(═O)—C₃F₇, —C(═S)—NH—CH₃, —C(═S)—NH—C₂H₅, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —C(═O)—NH—NH—CH₃, —C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂,—C(═O)—NH—N(CH₃)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —S(═O)₂-phenyl, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂, —(CH₂)-morpholinyl,—(CH₂)-piperidinyl, —(CH₂)-piperazinyl, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅), —S(═O)—NH₂, —S(═O)₂—NH—CH₃,—S(═O)₂—NH-phenyl, —NH—S(═O)₂—CH₃, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, phenyl, thiophenyl, phenoxy andbenzyl, whereby in each case the cyclic moieties cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, phenyl,thiophenyl, phenoxy and benzyl may optionally be substituted with 1, 2or 3 substituent(s) independently selected from the group consisting ofF, Cl, Br, methyl, ethyl and n-propyl;

a substituted radical selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl and morpholinyl, which issubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of thioxo (═S), —CH₂—OH, —CH₂—CH₂—OH,—CH₂—CH₂—CH₂—OH, —CH₂Cl, —CHCl₂, —C₂H₄Cl, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃,—S—C(CH₃)₃, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇,—C(═O)—O—C(CH₃)₃, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂,—O—C(═O)—CH₂—CH₂—CH₃, —O—C(═O)—C(CH₃)₃, —SCF₃, —SCF₂H, —SCFH₂, —SH,—SO₃H, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —CHO,—C(═O)—CF₃, —C(═O)—C₂F₅, —C(═O)—C₃F₇, —CF₂H, —CFH₂, —C(═O)—NH—NH—CH₃,—C(═O)—NH—NH—C₂H₅, —C(═O)—NH—NH₂, —C(═O)—NH—N(CH₃)₂, —S(═O)₂-phenyl,—(C₁₋₅-alkylene)-S—C₁₋₆-alkyl, —(C₁₋₅-alkylene)-S(═O)—C₁₋₆-alkyl,—(C₁₋₅-alkylene)-S(═O)₂—C₁₋₆-alkyl, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—N(CH₃)₂,—(CH₂)-morpholinyl, —(CH₂)-piperidinyl, —(CH₂)-piperazinyl,—(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂, —CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅),cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl,piperidinyl, thiophenyl, phenoxy and benzyl; whereby in each case thecyclic moieties cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,phenyl, pyrrolidinyl, piperidinyl, thiophenyl, phenoxy and benzyl canoptionally be substituted with 1, 2, 3, 4 or 5 substituent(s)independently selected from the group consisting of F, Cl, Br, I, —OH,—CF₃, —CN, —NO₂, —C₁₋₆-alkyl, —O—₁₋₆-alkyl, —O—CF₃ and —S—CF₃;

a radical selected from the group consisting of(1,2,3,4)-tetrahydronaphthyl, (2,3)-dihydro-1H-cyclopenta[b]indolyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl,cyclotridecyl, cyclotetradecyl, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, pyrrolidinyl, piperidinyl, piperazinyl,homopiperazinyl, morpholinyl, aziridinyl, azetidinyl, imidazolidinyl,thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl,azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl,(2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl,(2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl,tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl,(3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl,(1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl,[1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl,oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl, (1,3)-dioxolanyl,indolinyl, isoindolinyl, decahydronaphthyl,(1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl,octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl and norbornenyl, which is bonded via a —(CH₂)—,—(CH₂)—(CH₂)—, —(CH₂)—(CH₂)—(CH₂)— or —CH═CH-group and/or may optionallybe substituted with 1, 2, 3, 4 or 5 substituent(s) independentlyselected from the group consisting of oxo (═O), thioxo (═S), —CF₃,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl,tert-butyl, n-pentyl, 2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃,—O—CH₂—O—CH₃, —O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂,—C(OCH₃)(CH₃)₂, —S—CH₃, —S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂,—S—CH₂—CH₂—CH₂—CH₃, —S—(CH₃)₃, F, Cl, Br, I, —CN, —OCF₃, —SCF₃, —SCF₂H,—SCFH₂, —OH, —SH, —NO₂, —CHO, —C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C(CH₃)₃, —CF₂H, —CFH₂,—C(═O)—NH₂, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇,—C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇,—S(═O)₂—CH₃, —S(═O)₂—C₂H₅, —S(═O)₂—C₃H₅, —NH₂, —NH—CH₃, —NH—C₂H₅,—N(CH₃)₂, —N(C₂H₅)₂, cyclopentyl, cyclohexyl, pyrrolidinyl andpiperidinyl; and

R⁹, R¹⁰, R¹¹ and R¹², independently of one another, in each caserepresent a radical selected from the group consisting of methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,2-pentyl, 3-pentyl, neo-pentyl, n-hexyl, 2-hexyl, 3-hexyl, n-heptyl,2-heptyl, 3-heptyl, 4-heptyl, n-octyl, 2-octyl, 3-octyl, 4-octyl, vinyl,n-propenyl, n-butenyl, n-pentenyl, n-hexenyl, ethinyl, propinyl,n-butinyl, n-pentinyl and n-hexinyl, which may optionally be substitutedwith 1, 2, 3, 4, 5, 6, 7, 8 or 9 substituent(s) independently selectedfrom the group consisting of NH₂, —NH—C₃, —NH—C₂H₅, —N(CH₃)₂, —N(C₂H₅)₂,—NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃, —NH—C(═O)—O—CH₃,—NH—O(═O)—O—C₂H₅, —NH—C(═O)—O—C(CH₃)₃, —C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅,—C(═O)—NH—C(CH₃)₃, —C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —OH, —C(═O)—OH,—C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C(CH₃)₃, —C(═O)—CH₃, —C(═O)—C₂H₅and —C(═O)—C(CH₃)₃;

or a radical selected from the group consisting of phenyl, naphthyl,pyridinyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl imidazolyl, pyrazolyl, oxadiazolyl,thiadiazolyl, triazolyl, pyridazinyl, indolyl and isoindolyl, which maybe bonded via a —(CH₂)—, —(CH₂)—(CH₂)—, —(CH₂)—(CH₂)—(CH₂)— or—CH═CH-group and/or may optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of —CF₃,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl,tert-butyl, n-pentyl, 2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —S—CH₃,—S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, F,Cl, Br, I, —CN, —OCF₃, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —NO₂, —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —NH₂, —NH—CH₃, —NH—C₂H₅, —N(CH₃)₂,—N(C₂H₅)₂, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—C(CH₃)₂,—O—C(═O)—CH₂—CH₂—CH₃, —CH₂—N(CH₃)₂, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₃H₇)₂,—CH₂—N(C₄H₉)₂, —CH₂—N(CH₃)(C₂H₅) and —(CH₂)-morpholinyl;

optionally in form of one of its stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofits stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding N-oxide thereof, or a physiologicallyacceptable salt thereof, or a corresponding solvate thereof.

Particularly preferred are substituted pyrazoline compounds of generalformula I given above, wherein

R¹ represents a phenyl radical which may be substituted with 1, 2, 3, 4or 5 substituent(s) independently selected from the group consisting of—OH, F, Cl, Br, I, —O—CH₃ and —O—C₂H₅;

R² represents a phenyl radical which may be substituted with 1, 2, 3, 4or 5 substituent(s) independently selected from the group consisting ofF, Cl, Br and I;

R³ represents a radical selected from the group consisting ofaziridinyl, azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl,tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, 8-aza-spiro[4.5]decanyl and(2,3)-dihydro-1H-cyclopenta[b]-indolyl, which may optionally besubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of oxo (═O), thioxo (═S), methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂, —O—CH₃,—O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂CH₂—CH₃, —O—C(CH₃)₃,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—CH₂—O—CH₃, —CH₂—O—C₂H₅ and —OH; a substituted radical selected from thegroup consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl,cyclooctenyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyland morpholinyl, which is substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of—C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅,—C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃, —CH₂—O—CH₃, —CH₂—O—C₂H₅, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl,thiophenyl, phenoxy and benzyl;

a —NR⁴R⁵ moiety

or a —O—R⁶ moiety;

R⁴ represents a hydrogen atom;

R⁵ represents a radical selected from the group consisting of 2-pentyl,3-pentyl, neo-pentyl, 2-hexyl, 3-hexyl, 2-heptyl, 3-heptyl, 4-heptyl,2-octyl, 3-octyl, 4-octyl, 2-(6-methyl)-heptyl, 2-(5-methyl)-heptyl,2-(5-methyl)-hexyl, 2-(4-methyl)-hexyl, 2-(7-methyl)-octyl,2-(6-methyl)-octyl, —CH₂—N(CH₃)₂, —CH₂—N(C₂H₅)₂, —CH₂—CH₂—N(CH₃)₂,—CH₂—CH₂—N(C₂H₅)₂, —CH₂—CH₂—CH₂—N(CH₃)₂ and —CH₂—CH₂—CH₂—N(C₂H₅)₂;

a radical selected from the group consisting of adamantyl,bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl,(1,7,7)-trimethyl-bicyclo[2.2.1]heptyl, cyclononyl, cyclodecyl,cycloundecyl, cyclododecyl, cyclotridecyl and cyclotetradecyl;

a radical selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl,cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl, morpholinyl, aziridinyl,azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl,tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl andazocanyl, which is bonded via a —(CH₂)—, —(CH₂)—(CH₂)— or—(CH₂)—(CH₂)—(CH₂)-group;

a radical selected from the group consisting of aziridinyl, azetidinyl,imidazolidinyl, thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl,tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl,(2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl,(2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl,(2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl,(3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl,(1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl,(1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl,(5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl,(1,4)-dioxanyl, (1,3)-dioxolanyl, indolinyl, isoindolinyl,decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl,(1,2,3,4)-tetrahydroisoquinolinyl, octahydro-cyclopenta[c]pyrrolyl,(1,3,4,7,9a)-hexahydro-2H-quinolizinyl,(1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl,dodecahydro-carbazolyl, 9H-carbazolyl, decahydroisoquinolinyl,(6,7)-dihydro-4H-thieno[3,2-c]pyridinyl,(2,3)-dihydro-1H-benzo[de]isoquinolinyl,(1,2,3,4)-tetrahydroquinoxazlinyl, adamantyl,[1,2,3,4]-tetrahydronaphthyl, 8-aza-spiro[4.5]decanyl and(2,3)-dihydro-1H-cyclopenta[b]-indolyl, which may optionally besubstituted with 1, 2, 3, 4 or 5 substituent(s) independently selectedfrom the group consisting of oxo (═O), thioxo (═S), methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, n-pentyl,2-pentyl, n-hexyl, —CH₂—OH, —CH₂—CH₂—OH, —CH₂—CH₂—CH₂—OH, —O—CH₂—O—CH₃,—O—CH₂—CH₂—O—CH₃, —O—CH₂—O—C₂H₅, —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—O—CH₃, —O—C₂H₅, —O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃,—O—C(CH₃)₃, —C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇,—C(═O)—O—C(CH₃)₃, —CH₂—O—CH₃, —CH₂—O—C₂H₅ and —OH:

or a substituted radical selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl,pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl and morpholinyl,which is substituted with 1, 2, 3, 4 or 5 substituent(s) independentlyselected from the group consisting of —C(OCH₃)(C₂H₅)₂, —C(OCH₃)(CH₃)₂,—C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C₃H₇, —C(═O)—O—C(CH₃)₃,—CH₂—O—CH₃, —CH₂—O—C₂H₅, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, pyrrolidinyl, piperidinyl, thiophenyl, phenoxy, —O-Benzyl,and benzyl;

R⁶ represents a —P(═O)(OR⁹)₂ moiety; a —C(═O)—OR¹⁰ moiety; a—C(═O)—NH—R¹¹ moiety or a —C(═O)—R¹² moiety; and

R⁹, R¹⁰, R¹¹ and R¹², independently of one another, in each caserepresent a radical selected from the group consisting of methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,2-pentyl, 3-pentyl, neo-pentyl, n-hexyl, 2-hexyl, 3-hexyl, n-heptyl,2-heptyl, 3-heptyl, 4-heptyl, n-octyl, 2-octyl, 3-octyl, 4-octyl, vinyl,n-propenyl, n-butenyl, n-pentenyl, n-hexenyl, ethinyl, propinyl,n-butinyl, n-pentinyl and n-hexinyl, which may optionally be substitutedwith 1, 2, 3, 4, 5, 6, 7, 8 or 9 substituent(s) independently selectedfrom the group consisting of NH₂, —NH—CH₃, —NH—C₂H₅, —N(CH₃)₂,—N(C₂H₅)₂, —NH—C(═O)—CH₃, —NH—C(═O)—C₂H₅, —NH—C(═O)—C(CH₃)₃,—NH—C(═O)—O—CH₃, —NH—C(═O)—O—C₂H₅, —NH—C(═O)—O—C(CH₃)₃, —C(═O)—NH—CH₃,—C(═O)—NH—C₂H₅, —C(═O)—NH—C(CH₃)₃, —C(═O)—N(CH₃)₂, —C(═O)—N(C₂H₅)₂, —OH,—C(═O)—OH, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —C(═O)—O—C(CH₃)₃, —C(═O)—CH₃,—C(═O)—C₂H₅ and —C(═O)—C(CH₃)₃;

or a radical selected from the group consisting of phenyl, naphthyl,pyridinyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl,thiadiazolyl, triazolyl, pyridazinyl, indolyl and isoindolyl, which maybe bonded via a —(CH₂)—, —(CH₂)—(CH₂)—, —(CH₂)—(CH₂)—(CH₂)— or—CH═CH-group and/or may optionally be substituted with 1, 2, 3, 4 or 5substituent(s) independently selected from the group consisting of —CF₃,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl,tert-butyl, n-pentyl, 2-pentyl, n-hexyl, —O—CH₃, —O—C₂H₅,—O—CH₂—CH₂—CH₃, —O—CH(CH₃)₂, —O—CH₂—CH₂—CH₂—CH₃, —O—C(CH₃)₃, —S—CH₃,—S—C₂H₅, —S—CH₂—CH₂—CH₃, —S—CH(CH₃)₂, —S—CH₂—CH₂—CH₂—CH₃, —S—C(CH₃)₃, F,Cl, Br, I, —CN, —OCF₃, —SCF₃, —SCF₂H, —SCFH₂, —OH, —SH, —NO₂, —CHO,—C(═O)—CH₃, —C(═O)—C₂H₅, —C(═O)—C(CH₃)₃, —CF₂H, —CFH₂, —C(═O)—NH₂,—C(═O)—NH—CH₃, —C(═O)—NH—C₂H₅, —C(═O)—NH—C₃H₇, —C(═O)—N(CH₃)₂,—C(═O)—N(C₂H₅)₂, —S(═O)—CH₃, —S(═O)—C₂H₅, —S(═O)—C₃H₇, —S(═O)₂—CH₃,—S(═O)₂—C₂H₅, —S(═O)₂—C₃H₇, —NH₂, —NH—CH₃, —NH—C₂H₅, —N(CH₃)₂,—N(C₂H₅)₂, —O—C(═O)—CH₃, —O—C(═O)—C₂H₅, —O—C(═O)—CH(CH₃)₂,—O—C(═O)—CH₂—CH₂—CH₃, —CH₂—N(CH₃)₂, —(CH₂)—N(C₂H₅)₂, —CH₂—N(C₄H₉)₂,—CH₂—N(CH₃)(C₂H₅) and —(CH₂)-morpholinyl;

optionally in form of one of its stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofits stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding N-oxide thereof, or a physiologicallyacceptable salt thereof, or a corresponding solvate thereof.

More particularly preferred are substituted pyrazoline compounds ofgeneral formula I given above, wherein

R¹ represents a phenyl radical that is substituted with a hydroxy,fluorine, chlorine, bromine or iodine atom or a —O—CH₃-group in thepara-(4-)-position of the phenyl radical;

R² represents a (2,4)-dichloro-phenyl radical;

R³ represents a radical selected from the group consisting of

which is in each case bonded to the pyrazoline compound of generalformula I in any position of the cyclic part of the aforementionedradicals including the NH-groups, preferably said radicals are bonded tothe pyrazoline compound of general formula I at the nitrogen atom of thecyclic part of the aforementioned radicals;

or a —NR⁴R⁵ moiety;

R⁴ represents a hydrogen atom;

R⁵ represents a radical selected from the group consisting of 2-heptyl,3-heptyl, 4-heptyl, 2-octyl, 3-octyl, 4-octyl, —CH₂—N(CH₃)₂,—CH₂—N(C₂H₅)₂, —CH₂—CH₂—N(CH₃)₂, —CH₂—CH₂—N(C₂H₅)₂, —CH₂—CH₂—CH₂—N(CH₃)₂and —CH₂—CH₂—CH₂—N(C₂H₅)₂;

a radical selected from the group consisting of adamantyl,bicyclo[2.2.]heptyl, bicyclo[3.1.1]heptyl,(1,7,7)-trimethyl-bicyclo[2.2.1]heptyl, [1,2,3,4]-tetrahydronaphthyl,cyclononyl, cyclodecyl, cycloundecyl and cyclododecyl;

a radical selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, pyrrolidinyl,piperidinyl, piperazinyl, homopiperazinyl, morpholinyl, azepanyl,diazepanyl and azocanyl, which is bonded via a —(CH₂)—, —(CH₂)—(CH₂)— or—(CH₂)—(CH₂)—(CH₂)-group;

a substituted radical selected from the group consisting of cyclopentyl,cyclohexyl and cycloheptyl which is substituted with a —O-Benzylradical;

or a radical selected from the group consisting of

which is in each case bonded to the pyrazoline compound of generalformula I in any position of the cyclic part of the aforementionedradicals including the NH-groups, preferably said radicals are bonded tothe pyrazoline compounds of general formula I at the nitrogen atom ofthe cyclic part of the aforementioned radicals;

optionally in form of one of its stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofits stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding N-oxide thereof, or a physiologicallyacceptable salt thereof, or a corresponding solvate thereof.

Also more particularly preferred are substituted pyrazoline compounds ofgeneral formula L, M or N,

wherein

R^(L) represents H, —OH or oxo (═O);

R¹ represents a phenyl radical that is substituted with a hydroxy,fluorine, chlorine, bromine or iodine atom or a —O—CH₃-group in thepara-(4-)-position of the phenyl radical;

and R² represents a (2,4)-dichloro-phenyl radical;

optionally in form of one of its stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofits stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding N-oxide thereof, or a physiologicallyacceptable salt thereof, or a corresponding solvate thereof.

Most particularly preferred are substituted pyrazoline compounds ofgeneral formula I given above selected from the group consisting of

-   [10]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide-   [13]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid [2-(S)-1-methoxy-1-methyl-ethyl)-pyrrolidin-1-yl]-amide-   [14]    5-(4-Chloro-phenyl)-1-(2,4dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid [2-(R)-(1-methoxy-1-methyl-ethyl)-pyrrolidin-1-yl]-amide-   [15]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid [2-(1-methoxy-1-methyl-ethyl)-pyrrolidin-1-yl]-amide-   [16]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-ylamide-   [21]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(4-cyclohexyl-piperazin-1-yl)-methanone-   [24]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-amide-   [25]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1H,3H-benzo[de]isoquinolin-2-yl)-amide-   [26]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-cyclopentyl-piperazin-1-yl)-amide-   [27]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2-methyl-2,3-dihydro-indol-1-yl)-amide-   [28]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide-   [32]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cyclohexylmethyl-amide-   [35]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1methyl-hexyl)-amide-   [38]    Azocan-1yl-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-methanone-   [39]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(1,3-dihydro-isoindol-2-yl)-methanone-   [40]    Azetidin-1-yl-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-methanone-   [42]    [1,4′]Bipiperidin-1′-yl-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-methanone-   [44]    4-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carbonyl]-piperazine-1-carboxylic    acid ethyl ester-   [45]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone-   [48]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-carboxylic    acid (2,4-dioxo-imidazolidin-1-yl)-amide-   [49]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cyclododecylamide-   [52]    (4-Benzyl-piperazin-1-yl)-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-methanone-   [56]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-methanone-   [58]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide-   [63]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide-   [64]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-cyclopentyl-piperazin-1-yl)-amide-   [65]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1H,3H-benzo[de]isoquinolin-2-yl)-amide-   [66]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide hydrochloride-   [68]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-yl-amide-   [71]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2-morpholin-4-yl-ethyl)-amide-   [73]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (3-dimethylamino-propyl)-amide-   [74]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(3,6-dihydro-2H-pyridin-1-yl)-methanone-   [75]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(5,6-dihydro-4H-pyrimidin-1-yl)-methanone-   [76]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide-   [78]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(2,3-dihydro-1H-cyclopenta[b]indol-4-yl)-methanone-   [81]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone-   [84]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2-cyclohexyl-ethyl)-amide-   [85]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(dodecahydro-carbazol-9-yl)-methanone-   [87]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2-cyclopentyl-ethyl)-amide-   [88]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid bicyclo[2.2.1]hept-2-ylamide-   [91]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride-   [92]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-cyclopentyl-piperazin-1-yl)-amide-   [93]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1H,3H-benzo[de]isoquinolin-2-yl)-amide-   [94]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide-   [96]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-yl-amide-   [100]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide-   [101]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-cyclopentyl-piperazin-1-yl)-amide-   [102]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1H,3H-benzo[de]isoquinolin-2-yl)-amide-   [103]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide-   [1051]    1-(2,4-Dichloro-phenyl)-5-(4iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-ylamide;-   [109]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride-   [110]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-cyclopentyl-piperazin-1-yl)-amide-   [111]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (1H,3H-benzo[de]isoquinolin-2-yl)-amide-   [112]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide hydrochloride-   [114]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-ylamide hydrochloride-   [145]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azocan-1-ylamide hydrochloride-   [146]    5-(4-bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azocan-1-ylamide-   [147]    5-(4-fluoro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azocan-1-ylamide-   [148]    5-(4-methoxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azocan-1-ylamide-   [149]    5-(4-hydroxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azocan-1-ylamide hydrochloride-   [150]    5-(4-iodo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azocan-1-ylamide-   [151]    N-((1S,2S)-2-(benzyloxy)cyclohexyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [158]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-1-ylamide-   [159]    (R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-1-ylamide-   [160]    (S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-1-ylamide-   [161]    5-(4-bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-carboxylic    acid adamantan-1-ylamide-   [162]    5-(4-fluoro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-1-ylamide-   [163]    5-(4-methoxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-1-ylamide-   [164]    5-(4-hydroxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-1-ylamide-   [165]    5-(4-iodo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-1-ylamide-   [166]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-2-ylamide-   [167]    5-(4-bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-2-ylamide-   [168]    5-(4-fluoro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-2-ylamide-   [169]    5-(4-methoxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-2-ylamide-   [170]    5-(4-hydroxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-2-ylamide-   [171]    5-(4-iodo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid adamantan-2-ylamide-   [173]    1-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-ylamide hydrochloride-   [174]    1-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride-   [175]    1-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide hydrochloride-   [176]    (R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azocan-1-ylamide hydrochloride-   [177]    (S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azocan-1-ylamide hydrochloride-   [178]    N-((1R,2R)-2-(benzyloxy)cyclohexyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [179]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide hydrochloride-   [181]    (R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl amide hydrochloride-   [182]    (S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide hydrochloride-   [183]    (S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-ylamide hydrochloride-   [184]    (S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride-   [185]    (S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-ylamide-   [187]    (R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-ylamide hydrochloride-   [188]    (R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide-   [190]    (R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide-   [191]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cycloheptylmethyl-amide and-   [193]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride;    optionally in form of one of its stereoisomers, preferably    enantiomers or diastereomers, a racemate or in form of a mixture of    at least two of its stereoisomers, preferably enantiomers and/or    diastereomers, in any mixing ratio) or a corresponding N-oxide    thereof, or a physiologically acceptable salt thereof, or a    corresponding solvate thereof.

In another aspect the present invention relates to a compound selectedfrom the group consisting of

-   [7] N-oxide of    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide-   [8]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid morpholin-4-ylamide-   [9]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid morpholin-4-ylamide hydrochloride-   [11]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid pyrrolidin-1-ylamide-   [12]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,6-dimethyl-piperidin-1-yl)-amide-   [17]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-methyl-cyclohexyl)-amide-   [18]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2-methyl-cyclohexyl)-amide-   [19]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cycloheptylamide-   [20]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid hexylamide-   [23]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide-   [29]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid N′-butyl-N′-phenyl-hydrazide-   [30]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cyclobutylamide-   [31]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-tert-butyl-cyclohexyl)-amide-   [33]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid N-cyclohexyl-N-ethyl-amide-   [34]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cyclooctylamide-   [36]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cyclopropylamide-   [37]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cyclopentylamide-   [41]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cyclohexylamide-   [43]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(4-methyl-piperazin-1-yl)-methanone-   [46]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(2-methyl-piperazin-1-yl)-methanone-   [47]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid N-cyclohexyl-N-methyl-amide-   [50]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid diisopropylamide-   [51]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid dimethylamide-   [53]    1-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carbonyl]-pyrrolidine-2-carboxylic    acid-   [54]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-morpholin-4-yl-methanone-   [55]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cyclohexyl-isopropyl-amide-   [57]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (3-methyl-cyclohexyl)-amide-   [59]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(5-ethyl-2-methyl-piperidin-1-yl)-methanone-   [60]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide hydrochloride-   [61]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid pyrrolidin-1-ylamide-   [62]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,6-dimethyl-piperidin-1-yl)-amide-   [67]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid morpholin-4-ylamide-   [69]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid propylamide-   [70]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid tert-butylamide-   [72]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid butylamide-   [79]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (3,5-dimethyl-[1,2,4]triazol-4-yl)-amide-   [80]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(2,6-dimethyl-morpholin-4-yl)-methanone-   [82]    5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [83]    5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [86]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(4-propyl-piperidin-1-yl)-methanone-   [89]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid pyrrolidin-1-ylamide-   [90]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,6-dimethyl-piperidin-1-yl)-amide-   [95]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid morpholin-4-ylamide-   [97]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide-   [98]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid pyrrolidin-1-ylamide-   [99]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,6-dimethyl-piperidin-1-yl)-amide-   [104]    1-(2,4Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid morpholin-4-ylamide-   [106]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide hydrochloride-   [107]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid pyrrolidin-1-ylamide-   [108]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,6-dimethyl-piperidin-1-yl)-amide-   [113]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid morpholin-4-ylamide-   [130] 5-(4-Bromo    )-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid    cycloheptylamide-   [131]    5-(4-Fluorophenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cycloheptylamide-   [132]    5-(4-methoxyphenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cycloheptylamide-   [133]    5-(4-hydroxyphenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cycloheptylamide-   [134]    5-(4-iodophenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cycloheptylamide-   [135]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide hydrochloride-   [186]    (S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cycloheptylamide-   [189]    (R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid cycloheptylamide-   [192]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,6-dimethyl-piperidin-1-yl)-amide hydrochloride-   [194]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid pyrrolidin-1-ylamide hydrochloride-   [195]    [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(4-methyl-piperazin-1-yl)methanone    hydrochloride-   [136]    1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [137]    (R)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [138]    (S)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [139]    (R)-5-(4-chlorophenyl-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [140]    (S)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [141]    (R)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [142]    (S)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [143]    1-(2,4-dichlorophenyl)-5-(4-fluorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [144]    1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [152]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-oxo-piperidin-1-yl)-amide-   [153]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (3,6-dihydro-2H-pyridin-1-yl)-amide-   [154]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (3-hydroxy-piperidin-1-yl)-amide-   [155]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (4-hydroxy-piperidin-1-yl)-amide-   [156]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2-hydroxy-piperidin-1-yl)-amide-   [157]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (3,4-dihydro-2H-pyridin-1-yl)-amide [172]    1-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide hydrochloride-   [196]    (R)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [197]    (S)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [198]    (R)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [199]    (S)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [200]    5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3carboxamide-   [201]    5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H-pyrazole-3-carboxamide-   [202]    1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3carboxamide-   [203]    1-(2,4-dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide;    optionally in form of one of its stereoisomers, preferably    enantiomers or diastereomers, a racemate or in form of a mixture of    at least two of its stereoisomers, preferably enantiomers and/or    diastereomers, in any mixing ratio, or a corresponding N-oxide    thereof, or a physiologically acceptable salt thereof, or a    corresponding solvate thereof.

Another object of the present invention is a compound selected from thegroup consisting of

-   [115]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid methyl ester-   [116]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-carboxylic    acid methyl ester-   [117]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxyclic    acid methyl ester-   [118]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxyclic    acid methyl ester-   [119]    1-(2,4-Dichloro-phenyl)-5-(4iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxyclic    acid methyl ester-   [120]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid ethyl ester-   [121]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid ethyl ester-   [122]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazol-3-carboxyclic    acid ethyl ester-   [123]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxyclic    acid ethyl ester-   [124]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxyclic    acid ethyl ester-   [125]    1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxyclic    acid-   [126]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxyclic    acid-   [127]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxyclic    acid-   [128]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid and-   [129]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid-   [180]    1-(2,4Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid.

In another aspect the present invention relates to a compound selectedfrom the group consisting of

-   [60A]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide-   [66A]    5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide-   [82A]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2-(R)-hydroxy-cyclohexyl)-amide-   [83A]    5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2-(S)-hydroxy-cyclohexyl)-amide-   [91A]    1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide-   [106A]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid piperidin-1-ylamide-   [109A]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide-   [112A]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid (2,3-dihydro-indol-1-yl)-amide and-   [114A]    1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic    acid azepan-1-ylamide;    optionally in form of one of its stereoisomers, preferably    enantiomers or diastereomers, a racemate or in form of a mixture of    at least two of its stereoisomers, preferably enantiomers and/or    diastereomers, in any mixing ratio, or a corresponding N-oxide    thereof, or a physiologically acceptable salt thereof, or a    corresponding solvate thereof.

The afore mentioned compounds, e.g. the afore mentioned carboxylic acidsand carboxylic esters, are intermediates in the synthesis of compoundsof general formula I and in addition exhibit the same pharmacologicalactivity as the compounds of general formula I.

In another aspect the present invention also provides a process for thepreparation of substituted pyrazoline compounds of general formula Igiven above, wherein at least one compound of general formula II,

wherein R¹ has the meaning given above, is reacted with at least onecompound of general formula III,

or a corresponding salt thereof, wherein R² has the meaning given above,in a reaction medium, optionally in an inert atmosphere, optionally inthe presence of at least one acid, to yield at least one compound ofgeneral formula IV,

wherein R¹ and R² have the meaning given above, which is optionallyisolated and/or purified,

and at least one compound of general formula IV is reacted with anactivating agent in a reaction medium, optionally in an inertatmosphere, to yield at least one compound of general formula V,

wherein R¹ and R² have the meaning given above and A represents aleaving group, which is optionally purified and/or isolated,

and at least one compound of general formula V is reacted with at leastone compound of general formula R³—H, wherein R³ has the meaning givenabove, in a reaction medium, optionally in an inert atmosphere,optionally in the presence of at least one base selected from the groupconsisting of diisopropylethylamine, triethylamine, pyridine,dimethylaminopyridine and N-methylmorpholine, to yield at least onecompound of general formula i, wherein R¹, R² and R³ have the meaninggiven above, which is optionally purified and/or isolated;

or at least one compound of general formula IV is reacted with at leastone compound of general formula R³—H, wherein R³ represents a —NR⁴R⁵Moiety, wherein R⁴ and R⁵ have the meaning given above, in a reactionmedium, in the presence of at least one coupling agent, optionally inthe presence of at least one base, to yield at least one compound ofgeneral formula I, wherein R¹ and R² have the meaning given above and R⁴represents a —NR⁴R⁵ moiety, which is optionally purified and/orisolated.

Also preferred is the process for the preparation of a compound ofgeneral formula I given above, wherein at least one compound of generalformula R¹—C(═O)—H (general formula VII), wherein R¹ has the meaninggiven above, is reacted with at least one compound of general formulaVI,

wherein R^(1 represents a linear or branched C) ₁₋₆-alkyl radical, apotassium cation or a sodium cation, in a reaction medium, optionally inan inert atmosphere, optionally in the presence of at least one base, toyield at least one compound of general formula II,

wherein R¹ has the meaning given above, which is optionally purifiedand/or isolated,

and at least one compound of general formula II is reacted with anactivating agent in a reaction medium, optionally in an inertatmosphere, to yield at least one compound of general formula VIII,

wherein R¹ has the meaning given above and A represents a leaving group,which is optionally purified and/or isolated,

and at least one compound of general formula VIII is reacted with atleast one compound of general formula R³—H, wherein R³ has the, meaninggiven above, in a reaction medium, optionally in an inert atmosphere,optionally in the presence of at least one base selected from the groupconsisting of diisopropylethylamine, triethylamine, pyridine,dimethylaminopyridine and N-methylmorpholine, to yield at least onecompound of general formula IX,

wherein R¹ and R³ have the meaning given above, which is optionallypurified and/or isolated;

or at least one compound of general formula II is reacted with at leastone compound of general formula R³—H, wherein R³ represents a —NR⁴R⁵moiety, wherein R⁴ and R⁵ have the meaning given above, in a reactionmedium, in the presence of at least one coupling agent, optionally inthe presence of at least one base, to yield at least one compound ofgeneral formula IX, wherein PR³ represents a —NR⁴R⁵ moiety, which isoptionally purified and/or isolated,

and at least one compound of general formula IX is reacted with at leastone compound of general formula III,

wherein R² has the meaning given above, in a reaction medium, optionallyin an inert atmosphere, optionally in the presence of at least one acid,to yield at least one compound of general formula I, wherein R¹, R² andR³ have the meaning given above, which is optionally purified and/orisolated.

The inventive process is also illustrated in scheme I given below;

In step 1 a compound of general formula VI is reacted with a compound ofgeneral formula VII in a protic reaction medium, preferably in areaction medium selected from the group consisting of methanol, ethanol,isopropanol, n-butanol, water and mixtures thereof, in the presence ofat least one base, preferably in the presence of an alkali metalhydroxide such as sodium hydroxide or potassium hydroxide or an alkalimetal methoxide such as sodium methoxide, as described, for example, inSynthetic Communications, 26(11), 2229-33, (1996). The respectivedescription is hereby incorporated by reference and forms part of thedisclosure Reaction temperature as well as the duration of the reactionmay vary over a broad range. Preferred reaction temperatures range from−10° C. to the boiling point of the reaction medium. Suitable reactiontimes may vary for example from several minutes to several hours.

Preferably the reaction between a compound of general formula VI andgeneral formula VII can also be carried out under acid catalysedconditions, more preferably by refluxing the above mentioned compoundsin dichloromethane in the presence ofcopper(II)trifluoromethanesulfonate as described, for example, inSynlett, (1), 147-149, 2001. The respective description is herebyincorporated by reference and forms part of the disclosure.

In step 2 a compound of general formula II is reacted with a compound ofgeneral formula III in a reaction medium, preferably in a reactionmedium selected from the group consisting of methanol, ethanol,isopropanol, n-butanol, dieethylether, tert-butyl-methylether, dioxane,tetrahydrofuran or mixtures of at least two of these afore mentionedreaction media. Also preferably, said reaction may be carried out in thepresence of an acid, whereby the acid may be organic such as acetic acidand/or inorganic such as hydrochloric acid. Alternatively the reactionmay also be carried out in the presence of a base such as piperidine,piperazine, sodium hydroxide, potassium hydroxide, sodium methoxide orsodium ethoxide or mixtures of at least two of these bases.

Reaction temperature as well as the duration of the reaction may varyover a broad range. Suitable reaction temperatures range from roomtemperature, i.e. approximately 25° C. to the boiling point of thereaction medium. Suitable reaction times may vary for example fromseveral minutes to several hours.

In step 3 the carboxylic group of the compound of general formula IV maybe activated for further reactions by the introduction of a suitableleaving group according to conventional methods well known to thoseskilled in the art. Preferably the compounds of general formula IV aretransferred into an acid chloride, an acid anhydride, a mixed anhydride,a C₁₋₄ alkyl ester or an activated ester such as p-nitrophenylester.Suitable activating agent therefore are selected from the groupconsisting of thionyl chloride, oxalyl chloride and ethylchloroformate.

If said activated compound of general formula V is an acid chloride,wherein A represents a chlorine atom, that compound is preferablyprepared by the reaction of the corresponding acid of general formula IVwith thionyl chloride or oxalyl chloride, whereby said chlorinatingagent is also used as the reaction medium, in the presence of at leastone base, preferably in the presence of a base selected from the groupconsisting of triethylamine, N-methylmorpholine, pyridine,dimethylaminopyridine and diisopropylethylamine. Also preferably anadditional reaction medium may be used. Suitable reaction media includehydrocarbons such as benzene, toluenes or xylene, halogenatedhydrocarbons such as dichloromethane, chloroform or carbontetrachloride, ethers such as diethyl ether, dioxane, tetrahydrofuran ordimethoxyethane or dimethylformamide and mixtures thereof. Morepreferably toluene in the presence of a catalytic amount ofdimethylformamide is used as reaction medium, Preferred reactiontemperature range from 0° C. to the boiling point of the solvent andreaction times vary from several minutes to several hours.

If said activated compound of general formula V is a mixed anhydride,wherein A represents —O—C(═O)—O—C₂H₅, said anhydride may preferably beprepared, for example, by reaction of the corresponding acid of generalformula IV with ethylchloroformate in the presence of a base such astriethylamine, pyridine or diisopropylethylamine, in a suitable solventsuch as dichloromethane, optionally in an inert atmosphere, at atemperature between −50° C. and 50° C.

In step 4 the reaction between a compound of general formula V with acompound of general formula H—R³ to yield a compound of general formulaI, wherein R³ represents a —NR⁴R⁵ moiety, is preferably carried out inthe presence of a base such as triethylamine in a reaction medium suchas methylenchloride. The temperature is preferably in the range from 0°C. to the boiling point of the reaction medium. The reaction time mayvary over a broad range, e.g. from several hours to several days.

Alternatively the reaction of a compound of general formula V with acompound of general formula H—R³ to yield compounds of general formula Imay be carried out according to conventional methods well known to thoseskilled in the art, e.g. from Pascual, A., J. Prakt Chem., 1999, 341(7),695-700; Lin, S. et al., Heterocycles, 2001, 55(2), 265-277; Rao, P. etal., J. Org. Chem., 2000, 65(22), 7323-7344, Pearson D. E and Buehler,C. A., Synthesis, 1972, 533-542 and references cited therein. Therespective descriptions are hereby incorporated by reference and formpart of the present disclosure.

Preferably said reaction is carried out in the presence of a Lewis acid,which is preferably selected from the group consisting of FeCl₃, ZnCl₂and AlCl₃, in a suitable reaction medium such as toluene, benzene,tetrahydrofuran or similar reaction media. The temperature is preferablyin the range from 0° C. to the boiling point of the reaction medium,more preferably from 15 to 25° C. The reaction time may vary over abroad range, e.g. from several minutes to several hours.

In step 5 a compound of general formula IV is reacted with a compound ofgeneral formula H—R³, wherein R³ represents a —NR⁴R⁵ moiety, in areaction medium, preferably in a reaction medium selected from the groupconsisting of diethylether, tetrahydrofuran, acetonitrile, methanol,ethanol, (1,2)-dichlorethane, dimethylformamide, dichlormethane andmixtures therof, in the presence of at least one coupling agent,preferably in the presence of a coupling agent selected from the groupconsisting of 1-benzotriazolyloxy-tris-(dimethylamino)-phosphoniumhexafluorophosphate (BOP), dicyclohexylcarbodiimide (DCC),N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDCI),diisoproylcarbodiimide, 1,1′-carbonyl-diimidazole (CDI),N-[(dimethyamino)-1H-1,2,3-triazolo[4,5-b]pyridino-1-ylmethylen]-N-methylmethanaminiumhexafluorophosphate N-oxid (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniom hexafluorophosphate(HATU), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-tetrafluoroborate (TBTU), 1-hydroxy-benzotriazole (HOBt) and1-hydroxy-7-azabenzotrnazol (HOAt), optionally in the presence of abase, preferably in the presence of a base selected from the groupconsisting of pyridine, dimethylaminopyridine, N-methylmorpholine,triethylamine and diisopropylethylamine to yield a compound of generalformula I, wherein R³ represents a —NR⁴R⁵ moiety.

Preferably said reaction is carried out in the presence of EDCI andHOBt, optionally in the presence of N-methylmorpholine or triethylamine,in an aprotic reaction medium such as dimethylformamide ortetrahydrofuran, at a temperature between 20° C. and 30° C. for 15 to 24hours as described in Tetrahedron Lett. 2004, 45, 4977. The respectivedescription is hereby incorporated by reference and forms part of thedisclosure. Polymer-supported EDCI (P-EDCI) can also suitably be usedfor this process instead of EDCI as described in Tetrahedron Lett. 1998,39, 1487 and Tetrahedron Left, 2002, 43, 7685. The respectivedescriptions are hereby incorporated by reference and form part of thedisclosure.

Alternatively said reaction can be carried out by using HBTU in thepresence of a base such as diisopropylethylamine in an aprotic solvent,such as acetonitrile, preferably at a temperature between 20 and 30° C.for 15 to 24 hours.

A further inventive process to obtain compounds of general formula IV isillustrated in scheme II given below.

In step 1 a compound of general formula XI, wherein R¹ has the meaninggiven above and R″ represents a hydrogen atom or a C₁₋₆-alkyl radical,is reacted with a compound of general formula HS—R′″, wherein R′″represents an unsubstituted or at least mono-substituted phenyl radical,in a reaction medium, preferably in an dry aprotic reaction medium, morepreferably in toluene, optionally in the presence of an organic base,preferably in the presence of an organic base selected from the groupconsisting of triethylamine, pyridine, diisopropylethylamine,dimethylaminopyridine and N-methylmorpholine, preferably at atemperature between −50° C. and 50° C., preferably for 4 to 24 hours, toyield a compound of general formula XII, wherein R¹, R″ and R′″ have themeaning given above.

In step 2 a compound of general formula XII is reacted with a compoundof general formula III, wherein R² has the meaning given above, in areaction medium, preferably in a protic reaction medium, more preferablyin methanol, optionally in the presence of an inorganic base, preferablyin the presence of KHSO₄, preferably at a temperature between 0° C. and100° C., preferably for 4 to 15 hours, to yield a compound of generalformula XIII, wherein R¹, R², R″ and R′″ have the meaning given above.

In step 3 the compound of general formula XIII is cyclizedintramolecularly in a reaction medium, preferably in a dry aproticreaction medium, more preferably in dimethylformamide, preferably underan inert atmosphere, in the presence of a base, preferably in thepresence of a metal hydride salt, more preferably in the presence ofsodium hydride and/or potassium hydride to yield a compound of generalformula IV. If R″ represents a C₁₋₆-alkyl radical, the compound ofgeneral formula IV, wherein R″ represents a hydrogen atom, is obtainedafter saponification of the cyclized compound according to methods knownto those skilled in the art.

The sequence illustrated in scheme 1 is also described in, for example,Tetrahedron 2005, 81, 5235-5240 and Tetrahedron Asymmetry 2001, 12,1923-1928, The respective descriptions are hereby incorporated byreference and form part of the disclosure.

A compound of general formula IV can also be obtained as described inscheme fit given below.

The compound of general formula XIV, wherein R¹ has the meaning givenabove and R″ represents a hydrogen atom or a C₁₋₆-alkyl radical, isobtained by the bromination of a compound of general formula XI in areaction medium, preferably in an aprotic reaction medium, morepreferably in dichloromethane, with bromine at a temperature between 0°C. and 30° C. for several hours as described in Tetrahedron Lett. 1998,39 (44), 8163-8166; J. Chem. Soc. Perkin Trans 11 1999, 21, 3069-3070;Tetrahedron 1999, 55 (36), 11127-11142 and J. Heterocyclic Chem. 1986,23, 1199. The respective descriptions are hereby incorporated byreference and form part of the disclosure. Preferably a compound ofgeneral formula XIV is reacted with bromine in the presence of anaprotic solvent, preferably in the presence of dichloromethane, atambient temperature for 1 to 2 hours.

The compound of general formula XIV is reacted with a compound ofgeneral formula III, wherein R² has the meaning given above, andcyclized intramolecularly in a reaction medium, preferably in a dryaprotic reaction medium, more preferably in dimethylformamide or in amixture of dioxane, water and acetic acid, at a temperature between 0°C. and 250° C. to yield a compound of general formula IV as described inChemistry of Heterocyclic Compounds 1997, 33(6); Indian J. Chem. 208,1981, 1090: Indian J. Chem. 298, 1990, 887 and J. Indian Chem, Soc.1997, 74(3), 202-205. The respective descriptions are herebyincorporated by reference and form part of the disclosure, If R″represents a C₁₋₆-alkyl radical, the compound of general formula IV,wherein R″ represents a hydrogen atom, is obtained after saponificationof the cyclized compound according to methods known to those skilled inthe art.

A compound of general formula IV can also be obtained by the processdescribed in scheme IV.

An aldehyde of general formula VII, wherein R¹ has the meaning givenabove, is reacted with either a phosphonium ylide of general formula XV,a phosphine oxide of general formula XVI or a phosphonate of generalformula XVII, wherein in each case R″ represents a hydrogen atom or aC₁₋₆-alkyl radical and Z represents an unsubstituted or at leastmono-substituted phenyl radical, in a reaction medium, preferably in anaprotic reaction medium, more preferably in tetrahydrofuran, optionallyin the presence of at least one base, preferably in the presence of abase selected from the group consisting of potassium tert-butylat,n-butyllithium, sodium hydride and lithium diisopropylamide, to yield acompound of general formula XI which is reacted with a compound ofgeneral formula III, wherein R² has the meaning given above, andcyclized intramolecularly to yield a compound of general formula IV asdescribed above. The process is also described in Tetrahedron 1994, 50(44), 12727-12742 and Zhurnal Obshchei Khimii 1986, 56 (2), 347-353. Therespective descriptions are hereby incorporated by reference and formpart of the disclosure, If R″ represents a C₁₋₆-alkyl radical, thecompound of general formula IV, wherein R″represents a hydrogen atom, isobtained after saponification of the cyclized compound according tomethods known to those skilled in the art.

Another method for the preparation of compounds of general formula XI isillustrated in scheme V below.

A compound of general formula VII, wherein R¹ has the meaning givenabove, is reacted with a phosphonate of general formula XVIII, whereinR″″ represents a C₁₋₆-alkyl radical, preferably an ethyl radical, and acompound of general formula XIX, wherein R″ represents a hydrogen atomor a C₁₋₅-alkyl radical to yield a compound of general formula XI,wherein R¹ and R″ have the meaning given above. The process is describedin J. Chem. Soc. Perkin Trans 1, 1995, 741-742. Preferably the reactionis carried out by the addition of phosphonate of general formula XVII toa solution of n-butyllithium in a dry reaction medium, preferably intetrahydrofuran, at a temperature between −100° C. and −50° C., followedby the addition of N-phenylalcoxycarbonylacetimidoyl chloride of generalformula XIX and aldehyde of general formula VII and stirring at atemperature between 0° C. and 30° C. for several hours. The respectivedescription is hereby incorporated by reference and forms part of thedisclosure.

A compound of general formula IV can also be obtained according to theprocess described in scheme VI.

A compound of general formula VII, wherein R¹ has the meaning givenabove, is reacted with a compound of general formula XX, wherein R², hasthe meaning given above and R″″ represents a C₁₋₄-alkyl radical, isreacted in a reaction medium, preferably in ethanol, in the presence ofa base, preferably sodium acetate, at a temperature between 30° C. and90° C., or in a reaction medium, preferably in ethanol, in the presenceof glacial acetic acid at a temperature between 0° C. and 50° C. toyield a compound of general formula XXI, wherein R¹ and R² have themeaning given above and R″″ represents a C₁₋₆-alkyl radical. Thecompound of general formula XXI is converted into the compound ofgeneral formula IV in a reaction medium, preferably in ethanol and/orwater, in the presence of an acid, preferably in the presence ofhydrochloric acid, at a temperature between 50° C. and 120° C. to yielda compound of general formula IV. The process is described in J. Chem.Engineering Data 1984, 29(2), 225-229 and Indian J. Chem. 27B, 1988, 3,245-249. The respective descriptions are hereby incorporated byreference and form part of the disclosure.

A compound of general formula IV can also be obtained according to theprocess described in scheme VII,

A compound of general formula XXII, wherein R¹ has the meaning givenabove, is reacted with a compound of general formula XXIII, wherein R²has the meaning given above, R″″ represents a C₁₋₆-alkyl radical and Yrepresents a chlorine or bromine atom, in a reaction medium, preferablyin an aprotic or protic reaction medium, more preferably in tolueneand/or chloroform and/or ethanol, in the presence of a base, preferablyan organic base, more preferably an organic base selected from the groupconsisting of triethylamine, pyridine, diisopropylethylamine,dimethylaminopyridine, 1,4-diazabicyclo[2,2,2]octane andN-methylmorpholine, at a temperature between 0° C. and 150° C. to yielda compound of general formula IV. If regioisomers are obtained duringthe reaction, these regioisomers can be separated by conventionalchromatographic techniques. The compound of general formula IV, whereinR″″ represents a C₁₋₆-alkyl radical is converted into the correspondingacid by using standard methods which are known to those skilled in theart. The process is disclosed in Bull. Chem. Soc. Japan 1984, 57 (3),787-790 and Chem. Lett-1982, 543-546. The respective descriptions arehereby incorporated by reference and form part of the disclosure.

The compound of general formula XXIII can be prepared according to theprocesses described in scheme VII.

The compound of general formula XXIV, wherein R″″ represents aC₁₋₆-alkyl radical, is reacted in a reaction medium, preferably in amixture of water and ethanol, in the presence of at least one acidpreferably in the presence of acetic acid, at a temperature between 70°C. and 120° C. with a compound of general formula III, wherein R² hasthe meaning given above, to yield a compound of general formula XXV,wherein R² has the meaning given above and R″″ represents a C₁₋₆-alkylradical which is reacted with N-chloro-succinimide orN-bromo-succinimide in a reaction medium, preferably in an aproticreaction medium, more preferably in dimethylformamide at a temperaturebetween 0° C. and 30° C. to yield a compound of general formula XXIII.The process is described in Synth. Commun. 2001, 31(1), 111-115 andTetrahedron 1994, 50 (25), 7543-7556, The respective descriptions arehereby incorporated by reference and form part of the disclosure.

The compound of general formula XXIII can also be prepared by thereaction of a compound of general formula XXVI, wherein R″″ represents aC₁₋₆-alkyl radical, with a compound of general formula XXVII, wherein R²has the meaning given above and subsequent bromination of the resultingcompound of general formula XXVIII, wherein R² has the meaning givenabove and R″″ represents a C₁₋₆-alkyl radical, by using bromine in thepresence of acetic acid as described in Synthesis 1975, 333 and J. Chem.Soc. Perkin Trans. 1, 1977, 2092. The respective descriptions are herebyincorporated by reference and form part of the disclosure. The diazoniumsalt of general formula XXVII can preferably be obtained by the additionof an aqueous solution of sodium nitrite to a compound of generalformula R²—NH₂ in aqueous hydrochloride acid, wherein R² has the meaninggiven above. Alternatively this transformation can also be achieved inthe presence of a compound of general formula XXVI by adjusting the pHof the reaction medium to 4 by the addition of sodium acetate at atemperature between 0° C. and 30° C.

The compound of general formula XXIII can also be prepared by thereaction of a compound of general formula XXIX, wherein X has themeaning given above, R″″ represents a C₁₋₆-alkyl radical and Yrepresents a chlorine or bromine atom, with dimethylsulfide, in areaction medium, preferably in ethanol, at a temperature between 70° C.and 120° C. Optionally the dimethylsulfonium salt is isolated andfurther reacted with a compound of general formula XXVII, wherein R² hasthe meaning given above, in the presence of sodium acetate and aceticacid at a temperature between 0° C. and 30° C. as described inHeterocycles 1991, 32(6), 1101-1107. The respective description ishereby incorporated by reference and forms part of the disclosure.

The compound of general formula XXIII can also be prepared by thereaction of a compound of general formula XXXXVIII, wherein X has themeaning given above, R″″ represents a C₁₋₆-alkyl radical and Yrepresents a leaving group, preferably a leaving group selected from thegroup consisting of chlorine and bromine, with a compound of generalformula XXVII, wherein R² has the meaning given above, in the presenceof a protic solvent, preferably in the presence of a protic solventselected from the group consisting of methanol and ethanol, or in thepresence of an aprotic solvent, preferably in the presence oftetrahydrofuran, in the presence of a base, preferably in the presenceof sodium acetate, or in the presence of an acid, preferably in thepresence of acetic acid, The method is described in J, Chem. Soc. PerkinTransaction 1 1998, 24, 4103-4106; Tetrahedron Asymmetry 2000, 11(9),1975-1983; Tetrahedron 1998, 54(49), 14859-14868, Synthesis 1996, 9,1076-1078 and Synthesis 1995, 12, 1483-1484. The respective descriptionsare hereby incorporated by reference and form part of the disclosure.

Another method for the preparation of a compound of general formula IVis described in scheme IX.

A compound of general formula XXX, wherein R² has the meaning givenabove, Z represents an unsubstituted or at least mono-substituted phenylradical, preferably an unsubstituted phenyl radical, and R″″ representsa C₁₋₆-alkyl radical, preferably an ethyl radical, is reacted with acompound of general formula XXII, wherein R¹ has the meaning givenabove, in a reaction medium, preferably in xylene, at a temperaturebetween 50° C. and 200° C. for 2 to 30 hours to yield a compound ofgeneral formula IV. The process is described in Chem, Lett. 1983,507-510 and Bull. Chem. Soc. Japan 1984, 57(9), 2689-2690. Therespective descriptions are hereby incorporated by reference and formpart of the disclosure. The compound of general formula IV, wherein R″″represents a C₁₋₆-alkyl radical, is converted into the correspondingacid by using standard methods which are known to those skilled in theart.

A process for the preparation of a compound of general formula XXX isdescribed in scheme X.

A compound of general formula XXXI, wherein R″″ is a C₁₋₆-alkyl radical,is reacted with a compound of general formula Ill, wherein R² has themeaning given above, to yield a compound of general formula XXXII,wherein R² has the meaning given above and R″″ represents a C₁₋₆-alkylradical. Subsequently, the compound of general formula XXXIII is reactedwith phosphorous pentachlorde or POCl₃ in a reaction medium, preferablyin toluene, at a temperature between 0° C. and 50° C., followed by theaddition of a phenolic compound, preferably O-trimethylsilyl-p-cresol,in refluxing toluene to yield a compound of general formula XXX.

Another method for the preparation of a compound of general formula IVis described in scheme XI.

A compound of general formula XXXIII, wherein R¹ has the meaning givenabove and W represents —C(═O)—OH, —C(═O)—OR″″ or —CN, whereby R″″represents a C₁₋₆-alkyl radical, is converted to a compound of generalformula XXXIV, wherein R¹ and W have the meaning given above, by meansof epoxidation with a reagent selected from the group consisting ofperbenzoic acid, preferably m-chloro-perbenzoic acid, sodiumperoxocarbonate, hydrogen peroxide, dioxirane and hydroperoxide. Thecompound of general formula XXIV is reacted with a compound of generalformula III, wherein R² has the meaning given above, in a reactionmedium, preferably in ethanol, to yield a compound of general formulaXXXV, wherein R¹, R² and W have the meaning given above. Subsequently,the compound of general formula XXXV is converted into the correspondingxanthate of general formula XXXVI, wherein R¹, R² and W have the meaninggiven above, by reaction with an unsubstituted or at leastmono-substituted phenylthionochloroformate of general formulaZO—C(═S)—Cl, wherein Z represents an unsubstituted or at leastmono-substituted phenyl radical. The compound of general formula XXXVIis reacted with tributyltinhydride optionally followed by saponificationand/or hydrolysis to yield a compound of general formula IV, wherein R¹and R² have the meaning given above. The process is described in Synlett1990, 11, 705-706. The respective description is hereby incorporated byreference and forms part of the disclosure.

Yet another method for the preparation of a compound of general formulaIV is described in scheme XII.

A compound of general formula XXXVII, wherein R² has the meaning givenabove, is reacted with a compound of general formula XXXVIII, wherein R″represents a hydrogen atom or a C₁₋₆-alkyl radical, and a compound ofgeneral formula VII, wherein R¹ has the meaning given above, to yield acompound of general formula XXXIX, wherein R¹ and R² have the meaninggiven above and R″ represents a hydrogen atom or a C₁₋₆-alkyl radical.The compound of general formula XXXIX is converted into the compound ofgeneral formula XXXX by using O-substituted hydroxylamines according tothe method described in J. Org. Chem. 2002, 67, 6237-6239. Therespective description is hereby incorporated by reference and formspart of the disclosure. Alternatively, this transformation can beachieved by using nitrites and subsequent reduction according to methodsknown to those skilled in the art. Upon cyclization of a compound ofgeneral formula XXXX according to the methods described above a compoundof general formula IV is obtained, If R″ represents a C₁₋₆-alkylradical, the compound of general formula IV, wherein R″ representshydrogen, is obtained after saponification of the cyclized compoundaccording to methods known to those skilled in the art.

A further inventive process to obtain compounds of general formula IV isillustrated in scheme XIII given below,

The compound of general formula XXXXI, wherein R¹ has the meaning givenabove, is reacted with a compound of general formula XXXXII, wherein R″represents a hydrogen atom or a C₁₋₆-alkyl radical, in a reactionmedium, preferably in a dry aprotic reaction medium, more preferably intetrahydrofuran, in the presence of a catalyst, preferably in thepresence of a catalyst based on palladium, more preferably in thepresence of a catalyst selected from the group consisting of palladiumchloride [PdCl₂], palladium acetate [Pd(OAc)₂],tetrakistriphenylphosphin palladium [Pd(PPh₃)₄], bistriphenylphosphinpalladium dichloride [Pd(PPhi)₂Cl₂] and bistriphenylphosphin palladiumacetate [Pd(PPh₃)₂(OAc)₂], in the presence of a copper(I) salt,preferably in the presence of copper iodide, in the presence of a base,preferably in the presence of an organic base, more preferably in thepresence of an organic base selected from the group consisting oftriethylamine, N-methylmorpholine, pyridine, dimethylaminopyridine anddiisopropylethylamine, optionally in an inert atmosphere, at atemperature between 20° C. and 120° C. for 5 to 15 hours to yield acompound of general formula XI, wherein R¹ has the meaning given aboveand R″ represents a hydrogen atom or a C₁₋₆-alkyl radical. The compoundof general formula XI is without isolation and/or purification furtherreacted with a compound of general formula III, wherein R² has themeaning given above, at a temperature between 20° C. and 120° C. for 5to 10 hours. The process is described in Angew, Chem. Int, Ed. 2000,39(7), 1253-1256. The respective description is hereby incorporated byreference and forms part of the disclosure. If R″ represents aC₁₋₆-alkyl radical, the compound of general formula IV is obtained aftersaponification of the cyclized compound according to methods known tothose skilled in the art.

The compounds of general formula I, wherein R³ represents —NR⁴R⁵, canalso be obtained by the reaction sequence described in scheme XIV.

In step 1 a compound of general formula V is reacted with hydrazinehydrate in the presence of an aprotic or protic solvent, preferably inthe presence of ethanol, at reflux temperature to yield a compound ofgeneral formula XXXXIII, wherein R¹, R² and X have the meaning asdefined above.

In step 2 a compound of general formula XXXXIII is reacted with acompound of general formula XXXXIV, wherein R represents a hydrogen atomor a linear or branched C₁₋₁₂ alkyl radical and n is 0, 1, 2, 3, 4, 5,6, 7, 8, 9 or 10, in the presence of benzotriazole to yield a compoundof general formula XXXXV, wherein R, n, R¹, R² and X have the meaning asdefined above and Bt represents a benzotriazolyl radical. A compound ofgeneral formula XXXXV can be transformed into a compound of generalformula XXXXVI, wherein R, n, R¹, R² and X have the meaning as definedabove, in the presence of a reducing agent, preferably in the presenceof sodium borohydride, in the presence of an aprotic solvent, preferablyin the presence of tetrahydrofuran. Alternatively, the benzotriazolemoiety in compounds of general formula XXXXV can be replaced by a linearor branched C₁₋₁₀ alkyl group via reaction with the respective alkylGrignard reagents The process is disclosed J. Org. Chem. 1990, 55,3205-3209. The respective description is hereby incorporated byreference and forms part of the disclosure.

The compounds of general formula I, wherein R³ represents —NR⁴R⁵, canalso be obtained by the reaction sequence described in scheme XVI.

In step 1 a compound of general formula XXXXIII is reacted with acompound of general formula XXXXIV, wherein R represents a hydrogen atomor a linear or branched CA-₁₋₁₂ alkyl radical and n is 0, 1, 2, 3, 4, 5,6, 7, 8, 9 or 10, in the presence of a reducing agent, preferably in thepresence of a reducing agent selected from the group consisting ofsodium borohydride, sodium cyanoborohydride or triacetoxyborohydride, toyield a compound of general formula XXXXVI, wherein R, n, R¹, R² and Xhave the meaning as defined above,

In step 2 a compound of general formula XXXXIII is reacted with acompound of general formula XXXXVII, wherein R represents a hydrogenatom or a linear or branched C₁₋₁₂ alkyl radical, n is 0, 1, 2, 3, 4, 5,6, 7, 8, 9 or 10 and LG represents a leaving group, preferably a leavinggroup selected from the group consisting of chlorine and bromine, morepreferably LG represents bromine, in the presence of a base, preferablyin the presence of potassium carbonate, to yield a compound of generalformula XXXXVI, wherein R, n, R¹, R² and X have the meaning as definedabove.

The afore mentioned reactions involving the synthesis of the4,5-dihydro-pyrazole ring or the reaction of a compound comprising saidring are preferably carried out under an inert atmosphere, preferablyunder a nitrogen or argon atmosphere, to avoid oxidation of thering-system.

During some synthetic reactions described above the protection ofsensitive or reactive groups may be necessary and/or desirable. This canbe performed by using conventional protective groups like thosedescribed in Protective groups in Organic Chemistry, ed. J. F. W.McOmie, Plenum Press, 1973; T. W. Greene & P. G. M. Wuts and ProtectiveGroups in Organic Chemistry, John Wiley & sons, 1991. The respectiveparts of the description is hereby incorporated by reference and formspart of the disclosure. The protective groups may be eliminated whenconvenient by means well-known to those skilled in the art.

If the substituted pyrazoline compounds of general formula I areobtained in form of a mixture of stereoisomers, particularly enantiomersor diastereomers, said mixtures may be separated by standard proceduresknown to those skilled in the art, e.g. chromatographic methods orcrystallisation with chiral reagents. It is also possible to obtain purestereoisomers via stereoselective synthesis.

In a further aspect the present invention also provides a process forthe preparation of salts of substituted pyrazoline compounds of generalformula I and stereoisomers thereof, wherein at least one compound ofgeneral formula I having at least one basic group is reacted with atleast one inorganic and/or organic acid, preferably in the presence of asuitable reaction medium. Suitable reaction media include, for example,any of the ones given above. Suitable inorganic acids includehydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid,nitric acid, suitable organic acids are e.g. citric acid, maleic acid,fumaric acid, tartaric acid, or derivatives thereof, p-toluenesulfonicacid, methanesulfonic acid or camphersulfonic acid.

In yet a further aspect the present invention also provides a processfor the preparation of salts of substituted pyrazoline compounds ofgeneral formula I or stereoisomers thereof, wherein at least onecompound of general formula I having at least one acidic group isreacted with one or more suitable bases, preferably in the presence of asuitable reaction medium. Suitable bases are e.g. hydroxides, carbonatesor alkoxides, which include suitable cations, derived e.g. from alkalinemetals, alkaline earth metals or organic cations, e.g. [NH_(n)R_(4-n)]⁺,wherein n is 0, 1, 2, 3 or 4 and R represents a branched or unbranchedC₁₋₄-alkyl-radical. Suitable reaction media are, for example, any of theones given above.

In the presence of several acidic or basic groups, mono- or poly-saltsmay be formed. Compounds of the formula I having an acidic group, forexample a free carboxyl group, and a basic group, for example an aminogroup, may also be present in the form of inner salts, i.e., inzwitterionic form, or a part of the molecule may be present in the formof an inner salt and another part in the form of a normal salt.

Solvates, preferably hydrates, of the substituted pyrazoline compoundsof general formula l, of corresponding stereoisomers, of correspondingN-oxides or of corresponding salts thereof may also be obtained bystandard procedures known to those skilled in the art.

Substituted pyrazoline compounds of general formula I, which comprisenitrogen-atom containing saturated, unsaturated or aromatic rings mayalso be obtained in the form of their N-oxides by methods well known tothose skilled in the art.

The purification and isolation of the inventive substituted pyrazolinecompounds of general formula 1, of a corresponding stereoisomer, orsalt, or N-oxide, or solvate or any intermediate thereof may, ifrequired, be carried out by conventional methods known to those skilledin the art, e.g. chromatographic methods or recrystallisation

The compounds of general formula I given above may also act as prodrugs,i.e. they represent a drug precusor, which following administration to apatient releases a drug in vivo via some kind of chemical and/orphysiological process (e.g., a prodrug on being brought to aphysiological pH and/or through an enzyme action is converted to adesired drug form; see, e.g., R. B. Silverman, 19912, “The OrganicChemistry of Drug Design and Drug Action”, Academic Press, Chp. 8). Inparticular, the compounds of general formula I give rise to a compoundof general formula I, wherein R³ represents a —OH moiety, uponadministration to a patient.

Prodrugs can be used to alter the biodistribution (e.g., to allowcompounds which would not typically enter the reactive site of theprotease) or the pharmacokinetics for a particular compound. Forexample, a hydroxyl group, can be esterified, e.g., with a carboxylicacid group to yield an ester. When the ester is administered to asubject, the ester is cleaved, enzymatically or non-enzymatically,reductively or hydrolytically, to reveal the hydroxyl group.

The substituted pyrazoline compounds of general formula I given above,their stereoisomers, corresponding N-oxides, corresponding salts thereofand corresponding solvates are toxicologically acceptable and aretherefore suitable as pharmaceutical active substances for thepreparation of medicaments.

It has been found that the substituted pyrazoline compounds of generalformula I given above, stereoisomers thereof, N-oxides thereof,corresponding salts and corresponding solvates have a high affinity tocannabinoid receptors, particularly cannabinoid 1 (CB₁)-receptors, i,e.they are selective ligands for the (CB₁)-receptor and act as modulators,e.g. antagonists, inverse agonists or agonists, on these receptors. Inparticular, these pyrazoline compounds show little or no development oftolerance during treatment, particularly with respect to food intake,i.e. if the treatment is interrupted for a given period of time and thencontinued afterwards, the inventively used pyrazoline compounds willagain show the desired effect. After ending the treatment with thepyrazoline compounds, the positive influence on the body weight is foundto continue.

Furthermore, these substituted pyrazoline compounds show relatively weakHerg channel affinity, thus a low risk of prolongation of theQT-interval is to be expected for these compounds.

In summary, the inventively used substituted pyrazoline compounds aredistinguished by a broad spectrum of beneficial effects, while at thesame time showing relatively little undesired effects, i.e. effectswhich do not positively contribute to or even interfere with the wellbeing of the patient.

Thus, an other aspect of the present invention relates to a medicamentcomprising at least one substituted pyrazoline compound of generalformula I, optionally in form of one of its stereoisomers, preferablyenantiomers or diastereomers, a racemate or in form of a mixture of atleast two of its stereoisomers, preferably enantiomers and/ordiastereomers, in any mixing ratio, or a corresponding N-oxide thereof,or a physiologically acceptable salt thereof, or a corresponding solvatethereof, and optionally at least one physiologically acceptableauxiliary agent.

Preferably said medicament is suitable for the modulation (regulation)of cannabinoid-receptors, preferably cannabinoid 1 (CB₁) receptors, forthe prophylaxis and/or treatment of disorders of the central nervoussystem, disorders of the immune system, disorders of the cardiovascularsystem, disorders of the endocrinous system, disorders of therespiratory system, disorders of the gastrointestinal tract orreproductive disorders.

Particularly preferably said medicament is suitable for the prophylaxisand/or treatment of psychosis.

Also particularly preferably said medicament is suitable for theprophylaxis and/or treatment of food intake disorders, preferablybulimia, anorexia, cachexia, obesity and/or type II diabetus mellitus(non-insuline dependent diabetes mellitus), more preferably obesity. Theinventive medicament also seems to be active in the prophylaxis and/ortreatment of appetency disorders, e.g. the pyrazoline compounds ofgeneral formula I also reduce the desire for sweets.

Also particularly preferred is the use of at least one of the pyrazolinecompounds as defined herein and optionally one or more pharmaceuticallyacceptable excipients, for the preparation of a medicament for thetreatment of metabolic syndrome.

The metabolic syndrome and definitions thereof are described in detailby Eckel et at., The Lancet, Vol. 365 (2005), 1415-1428, includedherewith by reference, One of the respective definitions was establishedby the WHO in 1998 (as described in Alberti et al., Diabet. Med. 1998,15, pages 539-53, the respective description thereof is herewithincorporated by reference and forms part of the present disclosure). Theother, more widely accepted, definition of the metabolic syndrome wasestablished by the Adult Treatment Panel (ATP III) of the US NationalCholesterol Education Program (NCEP) in 2001, as described in JAMA 2001;285; 2486-97, the respective description thereof is herewithincorporated by reference and forms part of the present disclosure.

The metabolic syndrome is characterized by an interaction of severalphysiological parameters such as triglycerides, lipids, blood pressure,glucose levels and insuline levels.

Even though obesity may play a critical role in the development ofmetabolic syndrome, many of its aspects are weight independent,especially some lipid parameters. Especially the positive influence onthe weight independent aspects of the metabolic syndrome (see e.g.Pagotto and Pasquali, The Lancet, Vol. 365 (2005), 1363, 1364, includedherewith by reference) like some blood parameters, especially lipidparameters is one of the major and surprising advantages of theinventively used substituted pyrazoline compounds.

Another aspect of the invention is the use of one or more pyrazolinecompounds as defined herein for the manufacture of a medicament forimprovement of cardiovascular and/or metabolic risk factors, such as oneor more of the following factors:

-   Elevated triglycerides, whereby elevated levels of triglycerides are    preferably understood as being >150 mg/dl,-   Low HDL cholesterol, whereby low levels of HDL cholesterol are    preferably understood as being <40 mg/dl in men and <50 mg/dl in    women, Hypertension, whereby hypertension is preferably understood    as being >130/85 mmHg,-   Impaired fasting glucose, whereby impaired fasting glucose levels    are preferably understood as being >110 mg/dl,-   Insulin Resistance-   Dyslipidemia.

Another aspect of the invention is the use of one or more pyrazolinecompounds as defined herein for the manufacture of a medicament for thetreatment of the weight independent aspects of metabolic syndrome.

Another aspect of the invention is a method for improving cardiovascularand/or metabolic risk factors, such as one or more of the followingfactors:

-   Elevated triglycerides, whereby elevated levels of triglycerides are    preferably understood as being >150 mg/dl,-   Low HDL cholesterol, whereby low levels of HDL cholesterol are    preferably understood as being <40 mg/dl in men and <50 mg/dl in    women,-   Hypertension, whereby hypertension is preferably understood as    being >130/85 mmHg,-   Impaired fasting glucose, whereby impaired fasting glucose levels    are preferably understood as being >110 mg/dl,-   Insulin Resistance-   Dyslipidemia,-   in a subject, preferably a human.

Another aspect of the invention is a method for treating of the weightindependent aspects of metabolic syndrome.

Also particularly preferably said medicament is suitable for theprophylaxis and/or treatment of cancer, preferably for the prophylaxisand/or treatment of one or more types of cancer selected from the groupconsisting of brain cancer, bone cancer, lip cancer, mouth cancer,esophageal cancer, stomach cancer, liver cancer, bladder cancer,pancreas cancer, ovary cancer, cervical cancer, lung cancer, breastcancer, skin cancer, colon cancer, bowel cancer and prostate cancer,more preferably for the prophylaxis and/or treatment of one or moretypes of cancer selected from the group consisting of colon cancer,bowel cancer and prostate cancer.

Particularly preferably said medicament is suitable for the prophylaxisand/or treatment of alcohol abuse and/or alcohol addiction, nicotineabuse and/or nicotine addiction, drug abuse and/or drug addiction and/ormedicament abuse and/or medicament addiction, preferably drug abuseand/or drug addiction and/or nicotine abuse and/or nicotine addiction.

Thus, the inventive medicament is active in the treatment of abstinence,craving reduction and relapse prevention of alcohol intake. Theinventive medicament can also be used in the prophylaxis and/ortreatment of smoking addiction, cessation and/or dependence includingtreatment for craving reduction and relapse prevention of tobaccosmoking.

Medicaments and/or drugs, which are frequently the subject of misuseinclude opioids, barbiturates, cannabis, cocaine, amphetamines,phencyclidine, hallucinogens and benzodiazepines.

The medicament is also suitable for the prophylaxis and/or treatment ofone or more disorders selected from the group consisting of bonedisorders, preferably osteoporosis (e.g. osteoporosis associated with agenetic predisposition, sex hormone deficiency, or ageing),cancer-associated bone disease or Paget's disease of bone;schizophrenia, anxiety, depression, epilepsy, neurodegenerativedisorders, cerebellar disorders, spinocerebellar disorders, cognitivedisorders, cranial trauma, head trauma, stroke, panic attacks,peripheric neuropathy, inflammation, glaucoma. migraine, MorbusParkinson, Morbus Huntington, Morbus Alzheimer, Raynaud's disease,tremblement disorders, compulsive disorders, senile dementia, thymicdisorders, tardive dyskinesia, bipolar disorders, medicament-inducedmovement disorders, dystonia, endotoxemic shock, hemorrhagic shock,hypotension, insomnia, immunologic disorders, sclerotic plaques,vomiting, diarrhoea, asthma, memory disorders, pruritus, pain, or forpotentiation of the analgesic effect of narcotic and non-narcoticanalgesics, or for influencing intestinal transit.

The medicament is also suitable for the prophylaxis and/or treatment ofone or more disorders selected from the group consisting of dementia andrelated disorders, preferably for the prophylaxis and/or treatment ofone or more types of dementia selected from the group consisting ofmemory loss, vascular dementia, mild cognitive impairment,frontotemporal dementia and Pick's disease; binge eating disorders;juvenile obesity; drug induced obesity; atypical depression; behaviouraladdictions; attention deficit disorders; Tourette's syndrome;suppression of reward-related behaviours; e. g. conditioned placeavoidance such as suppression of cocaine- and morphine inducedconditioned place preference; impulsivity; sexual dysfunction;preferably for the prophylaxis and/or treatment of one or more types ofsexual dysfunction selected from the group consisting of erectiledifficulty and female sexual dysfunction; seizure disorders; nausea;emesis; neuroinflammatory disease, preferably for the prophylaxis and/ortreatment of one or more types of neuroinflammatory diseases selectedfrom the group consisting of multiple sclerosis, demyelinisation relateddisorders, Guillan-Barré syndrome, viral encephalitis andcerebrovascular accidents; neurological disorders; muscle spasticity;traumatic brain injury; spinal cord injury inflammation andimmunomodulatory disorders, preferably for the treatment and/orprophylaxis of one or more types of inflammation and immunomodulatorydisorders selected from the group consisting of cutaneous T-celllymphoma, rheumatoid arthritis, systemic lupus erythematosus, sepsis,sarcoidosis, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia,retinal disease, scleroderma, renal ischemia, mycocardial infarction,cerebral ischemia, nephritis, hepatitis, glomerulonephritis, cryptogenicfibrosing aveolitis, psoriasis, transplant rejection, atopic dermatitis,vasculitis, allergy, seasonal allergic rhinitis, Crohn's disease,inflammatory bowel disease, reversible airway obstruction, adultrespiratory distress syndrome, chronic obstructive pulmonary disease andbronchitis; cerebral apoplexy; craniocerebral trauma; neuropathic paindisorders; gastric ulcers; atherioscierosis and liver cirrhosis.

Another aspect of the present invention is the use of at least onesubstituted pyrazoline compound of general formula I given above assuitable active substances, optionally in form of one of thestereoisomers, preferably enantiomers or diastereomers, a racemate or inform of a mixture of at least two of the stereoisomers, preferablyenantiomers and/or diastereomers, in any mixing ratio, or acorresponding N-oxide thereof, or a corresponding salt thereof, or acorresponding solvate thereof and optionally one or morepharmaceutically acceptable excipients, for the preparation of amedicament for the modulation of cannabinoid-receptors, preferablycannabinoid 1 (CB₁) receptors, for the prophylaxis and/or treatment ofdisorders of the central nervous system, disorders of the immune system,disorders of the cardiovascular system, disorders of the endocrinoussystem, disorders of the respiratory system, disorders of thegastrointestinal tract or reproductive disorders.

Particularly preferred is the use of at least one of the respectivesubstituted pyrazoline compounds, optionally in form of one of thestereoisomers, preferably enantiomers or diastereomers, a racemate or inform of a mixture of at least two of the stereoisomers, preferablyenantiomers and/or diastereomers, in any mixing ratio, or acorresponding N-oxide thereof or a corresponding salt thereof, or acorresponding solvate thereof, and optionally one or morepharmaceutically acceptable excipients, for the preparation of amedicament for the prophylaxis and/or treatment of psychosis.

Also particularly preferred is the use of at least one of the respectivesubstituted pyrazoline compounds, optionally in form of one of thestercoisomers, preferably enantiomers or diastereomers, a racemate or inform of a mixture of at least two of the stereoisomers, preferablyenantiomers and/or diastereomers, in any mixing ratio, or acorresponding N-oxide thereof or a corresponding salt thereof, or acorresponding solvate thereof, and optionally one or morepharmaceutically acceptable excipients, for the preparation of amedicament for the prophylaxis and/or treatment of food intakedisorders, preferably bulimia, anorexia, cachexia, obesity and/or typeii diabetus mellitus (non-insuline dependent diabetes mellitus), morepreferably obesity

Also particularly preferred is the use of at least one of the respectivesubstituted pyrazoline compounds, optionally in form of one of thestereoisomers, preferably enantiomers or diastereomers, a racemate or inform of a mixture of at least two of the stereoisomers, preferablyenantiomers and/or diastereomers, in any mixing ratio, or acorresponding N-oxide thereof, or a corresponding salt thereof, or acorresponding solvate thereof, and optionally one or morepharmaceutically acceptable excipients, for the preparation of amedicament for the prophylaxis and/or treatment of cancer, preferablyfor the prophylaxis and/or treatment of one or more types of cancerselected from the group consisting of brain cancer, bone cancer, lipcancer, mouth cancer, esophageal cancer, stomach cancer, liver cancer,bladder cancer, pancreas cancer, ovary cancer, cervical cancer, lungcancer, breast cancer, skin cancer, colon cancer, bowel cancer andprostate cancer, more preferably for the prophylaxis and/or treatment ofone or more types of cancer selected from the group consisting of coloncancer, bowel cancer and prostate cancer.

Also particularly preferred is the use of at least one of the respectivesubstituted pyrazoline compounds, optionally in form of one of thestereoisomers, preferably enantiomers or diastereomers, a racemate or inform of a mixture of at least two of the stereoisomers, preferablyenantiomers and/or diastereomers, in any mixing ratio, or acorresponding N-oxide thereof, or a corresponding salt thereof, or acorresponding solvate thereof, and optionally one or morepharmaceutically acceptable excipients, for the preparation of amedicament for the prophylaxis and/or treatment of alcohol abuse and/oralcohol addiction, nicotine abuse and/or nicotine addiction, drug abuseand/or drug addiction and/or medicament abuse and/or medicamentaddiction, preferably drug abuse and/or drug addiction and/or nicotineabuse and/or nicotine addiction.

Medicaments/drugs, which are frequently the subject of misuse includeopioids, barbiturates, cannabis, cocaine, amphetamines, phencyclidine,hallucinogens and benzodiazepines.

Also preferred is the use of at least one of the respective substitutedpyrazoline compounds, optionally in form of one of the stereoisomers,preferably enantiomers or diastereomers, a racemate or in form of amixture of at least two of the stereoisomers, preferably enantiomersand/or diastereomers, in any mixing ratio, or a corresponding N-oxidethereof, or a corresponding salt thereof, or Em corresponding solvatethereof, and optionally one or more pharmaceutically acceptableexcipients, for the preparation of a medicament for the prophylaxisand/or treatment of one or more disorders selected from the groupconsisting of bone disorders, preferably osteoporosis (e.g, osteoporosisassociated with a genetic predisposition, sex hormone deficiency, orageing), cancer-associated bone disease or Paget's disease of bone;schizophrenia, anxiety, depression, epilepsy, neurodegenerativedisorders, cerebellar disorders, spinocerebellar disorders, cognitivedisorders, cranial trauma, head trauma, stroke, panic attacks,peripheric neuropathy, inflammation, glaucoma, migraine, MorbusParkinson, Morbus Huntington, Morbus Alzheimer, Raynaud's disease,tremblement disorders, compulsive disorders, senile dementia, thymicdisorders, tardive dyskinesia, bipolar disorders, medicament-inducedmovement disorders, dystonia, endotoxemic shock, hemorrhagic shock,hypotension, insomniac immunologic disorders, sclerotic plaques,vomiting, diarrhoea, asthma, memory disorders, pruritus, pain, or forpotentiation of the analgesic effect of narcotic and non-narcoticanalgesics, or for influencing intestinal transit.

Also particularly preferred is the use of at least one of the respectivesubstituted pyrazoline compounds, optionally in form of one of thestereoisomers, preferably enantiomers or diastereomers, a racemate or inform of a mixture of at least two of the stereoisomers, preferablyenantiomers and/or diastereomers, in any mixing ratio, or acorresponding solvate thereof, and optionally one or morepharmaceutically acceptable excipients, for the preparation of amedicament for the prophylaxis and/or treatment of one or more disordersselected from the group consisting of dementia and related disorders,preferably for the prophylaxis and/or treatment of one or more types ofdementia selected from the group consisting of memory loss, vasculardementia, mild cognitive impairment, frontotemporal dementia and Pick'sdisease; binge eating disorders; juvenile obesity; drug induced obesity;atypical depression; behavioural addictions; attention deficitdisorders; Tourette's syndrome; suppression of reward-relatedbehaviours; e.g. conditioned place avoidance such as suppression ofcocaine- and morphine induced conditioned place preference; impulsivity;sexual dysfunction; preferably for the prophylaxis and/or treatment ofone or more types of sexual dysfunction selected from the groupconsisting of erectile difficulty and female sexual dysfunction; seizuredisorders; nausea; emesis; neuroinflammatory disease, preferably for theprophylaxis and/or treatment of one or more types of neuroinflammatorydiseases selected from the group consisting of multiple sclerosis,demyelinisation related disorders, Guillan-Barré syndrome, viralencephalitis and cerebrovascular accidents; neurological disorders;muscle spasticity; traumatic brain injury; spinal cord injury;inflammation and immunomodulatory disorders, preferably for thetreatment and/or prophylaxis of one or more types of inflammation andimmunomodulatory disorders selected from the group consisting ofcutaneous T-cell lymphoma, rheumatoid arthritis, systemic lupuserythematosus, sepsis, sarcoidosis, idiopathic pulmonary fibrosis,bronchopulmonary dysplasia, retinal disease, scleroderma, renalischemia, mycocardial infarction, cerebral ischemia, nephritis,hepatitis, glomerulonephritis, cryptogenic fibrosing aveolitis,psoriasis, transplant rejection, atopic dermatitis, vasculitis, allergy,seasonal allergic rhinitis, Crohn's disease, inflammatory bowel disease,reversible airway obstruction, adult respiratory distress syndrome,chronic obstructive pulmonary disease and bronchitis; cerebral apoplexy;craniocerebral trauma; neuropathic pain disorders; gastric ulcers;atheriosclerosis and liver cirrhosis.

Dementia is a disease characterized by the progressive deterioration incognitive and social adaptive functions that can eventually interferewith the patient's ability to live independently. Dementia alsoconstitutes of impairment in short- and long-term memory plus additionalsymptoms, such as problems with abstract thinking, judgment, orpersonality. An estimated 18 million patients suffer from dementiaworldwide. The most common forms of dementia include Alzheimer's diseaseand vascular dementia. Other forms are frontotemporal dementia andPick's disease.

Dementia can also be of vascular origin. Vascular dementia(atherosclerotic cerebrovascular disease) is considered to be the secondmost common dementia of late life, affecting approximately 10-15% of allcases. AD and vascular dementia can exist in isolation or together(mixed dementia). In vascular dementia, atherosclerotic changes incerebral vessels can lead to reduced local blood flow that results inmultiple small strokes (multi-infarct dementia). Vascular dementia ispharmacologically treated by stroke prophylaxis, and by treatment of thecognitive deficit.

Alzheimer's disease (AD), the most common and important form ofdementia, is a neurodegenerative disorder that is characterized byprogressive impairment of cognitive functions, such as abstractreasoning and memory. Currently, an estimated 2 million people in theUnited States and 12 million worldwide are afflicted by this disease.Due to increasing life expectancy, it is predicted that there will beover 100 million AD patients worldwide by the year 2050 AD is one of themost prevalent illnesses in the elderly The majority of AD patients arein their sixties or older. More than 5% of all persons over the age of70 have significant memory loss due to AD.

AD is mainly characterized through a gradual development offorgetfulness. In further advanced disease stages, other failures incerebral function become increasingly apparent. This includes impairmentof speech, writing, and arithmetic skills. Visiospacial orientation,such as parking the car, dressing properly, and giving and understandingdirections to a location, can become defective or impaired. In latestage disease, patients forget how to use common objects and tools whileretaining necessary motor power and co-ordination for these activities.

Schizophrenia is characterized by profound disruption in cognition andemotion, affecting the most fundamental human attributes; language,thought, perception, affect, and sense of self. Positive symptomsinclude psychotic manifestations, such as hearing internal voices orexperiencing other sensations not connected to an obvious source(hallucinations) and assigning unusual significance or meaning to normalevents or holding fixed false personal beliefs (delusions). Negativesymptoms are characterized by affective flattening and lack ofinitiative or goals (avolition), loss of usual interests or pleasures(anhedonia), disturbances of sleep and eating, dysphoric mood(depressed, anxious, irritable, or angry mood) and difficultyconcentrating or focusing attention.

Major depression is a multifaceted disorder characterized by primarilyby dysphoric mood and loss of interest or pleasure in activities thatwere once enjoyable. Other physical and psychological symptoms includeinability to concentrate, motor disturbances (psychomotor retardation oragitation), feelings of worthlessness, inappropriate guilt, thoughts ofsuicide, and disturbances in appetite and sleep.

Anxiety disorders are a group of syndromes that include generalizedanxiety disorder, panic disorder, phobias, obsessive-compulsivedisorder, and post traumatic stress disorder. Although each disorder hasits own distinct features, all share common symptoms of excessiveworrying, intense fears and dread, hypervigilance and/or somaticsymptoms, in the absence of a dangerous situation.

Normal sexual function requires, among others, the ability to achieveand maintain penile erection. Major anatomic structures of the penisthat arc involved in erectile function include the corpus cavernosum,corpus spinosum, and the tunica albuginea (a collagenous sheath thatsurrounds each corpus). Thecorpora are composed of a mass of smoothmuscle (trabecula) which contains a network of endothelial-lined vessels(lacunar spaces). Penile tumescence and erection is caused by relaxationof the arteries and corporal smooth muscles, while closing emissaryveins, leading to increased blood flow into the lacunar network. Centraland peripheral innervation contributes to regulation of the erectileresponse.

Erectile dysfunction (ED) may result from failure to initiate, fill, orstore adequate blood volume within the lacunar network of the penis.Depending on the underlying dysfunction, ED may be vasculogenic,neurogenic, endocrinologic, diabetic, psychogenic, ormedication-related.

ED affects 10-25% of middle-aged and elderly men, and has a profoundimpact on the well-being of affected men. It is currently treated usingPDE5 inhibitors such as vardenafil, tadalifil, and sildenafil.Intraurethral alpostadil (prostaglandin El) may be used in patients thatfail on oral agents. In addition, vacuum constriction devices (VCD) area well-established, noninvasive therapy.

Female sexual dysfunction (FSD) is highly prevalent, age-related, andprogressive. It affects 30 to 50% of women. FSD denotes a range ofmedical problems and is categorized according to disorders of (1)desire, (2) arousal, (3) orgasm and (4) sexual pain, and symptomsinclude diminished vaginal lubrication, pain and discomfort withintercourse, decreased arousal, and difficulty achieveing orgasm. On amolecular level, vasoactive intestinal peptide (VIP), nitic oxide (NO),and sex hormones such as estrogens and androgens have been suggested tobe important in female sexual function. Current treatment approachesinclude estrogen replacement therapy, methyl testosterone, PDE5inhibitors such as sildenafil, the NO-donor L-arginine, prostaglandinEl, phentolamine, and the dopamine agonists apomorphine.

The medicament according to the present invention may be in any formsuitable for the application to humans and/or animals, preferably humansincluding infants, children and adults and can be produced by standardprocedures known to those skilled in the art. The medicament can beproduced by standard procedures known to those skilled in the art, e.g.from the table of contents of “Pharmaceutics: The Science of DosageForms”, Second Edition, Aulton, M. E. (ED. Churchill Livingstone,Edinburgh (2002); “Encyclopedia of Pharmaceutical Technology”, SecondEdition, Swarbrick, J. and Boylan J. C. (Eds.), Marcel Dekker, Inc. NewYork (2002); “Modern Pharmaceutics”, Fourth Edition, Banker G. S. andRhodes C. T. (Eds.) Marcel Dekker, Inc. New York 2002 y “The Theory andPractice of Industrial Pharmacy”, Lachman L., Lieberman H. And Kanig J.(Eds.), Lea & Febiger, Philadelphia (1986). The respective descriptionsare: hereby incorporated by reference and form part of the disclosure.The composition of the medicament may vary depending on the route ofadministration.

The medicament of the present invention may for example be administeredparentally in combination with conventional injectable liquid carriers,such as water or suitable alcohols. Conventional pharmaceuticalexcipients for injection, such as stabilising agents, solubilizingagents, and buffers, may be included in such injectable compositions.These medicaments may for example be injected intramuscularly,intraperitoneally, or intravenously.

Medicaments according to the present invention may also be formulatedinto orally administrable compositions containing one or morephysiologically compatible carriers or excipients, in solid or liquidform. These compositions may contain conventional ingredients such asbinding agents, fillers, lubricants, and acceptable wetting agents. Thecompositions may take any convenient form, such as tablets, pellets,granules, capsules, lozenges, aqueous or oily solutions, suspensions,emulsions, or dry powdered forms suitable for reconstitution with wateror other suitable liquid medium before use, for immediate or retardedrelease. The multiparticulate forms, such as pellets or granules, maye.g. be filled into a capsule, compressed into tablets or suspended in asuitable liquid.

Suitable controlled release formulations, materials and methods fortheir preparation are known from the prior art, e.g. from the table ofcontents of “Modified-Release Drug Delivery Technology”, Rathbone, M. J.Hadgraft. J. and Roberts, M. S. (Eds.), Marcel Dekker, Inc., New York(2002); “Handbook of Pharmaceutical Controlled Release Technology”,Wise, D. L. (Ed.), Marcel Dekker, Inc. New York, (2000); “ControlledDrug Delivery”, Vol, 1, Basic Concepts, Bruck, S. D. (Ed.), CRD PressInc., Boca Raton (1983) y de Takada, K. and Yoshikawa, H., “Oral DrugDelivery”, Encyclopedia of Controlled Drug Delivery, Mathiowitz, E.(Ed.), John Wiley & Sons, Inc., New York (1999), Vol. 2, 728-742; Fix,J., “Oral drug delivery, small intestine and colon”, Encyclopedia ofControlled Drug Delivery, Mathiowitz, E. (Ed.), John Wiley & Sons, Inc.,New York (1999), Vol. 2, 698-728. The respective descriptions are herebyincorporated by reference and form part of the disclosure.

Medicaments according to the present invention may also comprise anenteric coating, so that their dissolution is dependent on pH-value. Dueto said coating the medicament can pass the stomach undissolved and therespective pyrazoline compound of general formula I is liberated in theintestinal tract. Preferably the enteric coating is soluble at a pHvalue of 5 to 7.5. Suitable materials and methods for the preparationare known from the prior art.

Typically, the medicaments according to the present invention maycontain 1-60% by weight of one or more substituted pyrazoline compoundsas defined herein and 40-99% by weight of one or more auxiliarysubstances (additives).

The liquid oral forms for administration may also contain certainadditives such as sweeteners, flavoring, preservatives, and emulsifyingagents. Non-aqueous liquid compositions for oral administration may alsobe formulated, containing edible oils. Such liquid compositions may beconveniently encapsulated in e.g., gelatin capsules in a unit dosageamount.

The compositions of the present invention may also be administeredtopically or via a suppository.

The daily dosage for humans and animals may vary depending on factorsthat have their basis in the respective species or other factors, suchas age, sex, weight or degree of illness and so forth. The daily dosagefor humans may preferably be in the range from 1 to 2000, preferably 1to 1500, more preferably 1 to 1000, even more preferably 1 to 150milligrams of active substance to be administered during one or severalintakes per day.

Pharmacological Methods

I. In-Vitro Determination of Affinity to CBI/CB2-Receptors

a)

The in-vitro determination of the affinity of the inventive substitutedpyrazoline compounds to CB₁/CB₂-Rezeptors is carried out as described inthe publication of Ruth A. Ross, Heather C. Brockie et al.,“Agonist-inverse agonist characterization at CB₁ and CB₂ cannabinoidreceptors of L-759633, L759656 and AM630”, British Journal ofPharmacology, 126, 665-672, (1999), whereby the transfected human CB₁and CB₂ receptors of Receptor Biology, Inc. are used. The radioligandused for both receptors is [³H]-CP55940. The respective parts of thedescription is hereby incorporated by reference and forms part of thepresent disclosure.

b)

Rat cerebellum CB1 binding

Binding affinity to CB1 receptor was evaluated according to amodification of the method described by Govaerts et al., Eur J PharmacSci 23, 233-243 (2004). The respective parts of the description ishereby incorporated by reference and forms part of the presentdisclosure

Briefly, cerebellum from male wistar rats (250-300 g) were carefullydissected on ice and homogenates were prepared with Potter-Helveheim ina cold 50 mM Tris-HCl solution containing 5 mM MgCl₂, 1 mM EDTA and 0.25M sucrose, pH 7.4. The suspension was centrifuged at 1,000×g for 5minutes. The supernatants were collected and centrifuged 50.000×g for 15minutes. The resulting pellets were then resuspended in Tris-HCl bufferwithout sucrose, homogenized and incubated for 15 min at 37° C. in anorbital shaker bath and centrifuged again at 50,000×g for 15 min.Pellets were weighted resuspended in Tris-HCl buffer without sucrose,homogenized with Ultraturrax at 13,500 rpm for 3×5 seconds and alicuotedin 0.9 ml volumes in Eppendorf tubes. Alicuotes were centrifuged at20,800×g for 5 minutes, supernatants discarded and pellets were frozenat −80° C. until use. Total protein concentration was determined usingthe Bio-Rad Lowry method based kit. Competitive binding experiments wereperformed in presence of 1 nM [³-H]-CP 55,940 in siliconized glass tubescontaining 100 μg protein/tube resuspended in 1 ml final volume of 50 mMTris-HCl, 5 mM MgCl₂, 1 mM EDTA, 0.5% (wlv) bovine serum albumin, pH7.4. Compounds were present at various concentrations and the nonspecific binding was determined in the presence of 10 μM HU-210. After 1hour incubation at 30° C., the suspension was rapidly filtered through0.5% PEI pre-treated GF/B fiber filters on a 96-well harvester andwashed 3 times with 3 ml ice-cold binding buffer without bovine serumalbumin. Radioactivity on filters was measured with Wallac Winspectral1414 counter by liquid scintillation in 6 ml Ecosdint H (NationalDiagnostics, U.K.). Assays were made in triplicates.

Binding data were analyzed by non-linear regression with the softwareGraphPad Prism Version 3.03.

II. In-Vivo Bioassay System for Determination of Cannabinoid Activity

Mouse Tetrad Model

Substances with affinity for cannabinoid receptors are known to producea wide range of pharmacological effects. It is also known thatintravenous administration of a substance with affinity for cannabinoidreceptors in mice produces analgesia, hypothermia, sedation andcatalepsy Individually, none of these effects can be considered as proofthat a tested substance has affinity for cannabinoid-receptors, sinceall of these effects are common for various classes of centrally activeagents. However, substances, which show all of these effects, i.e.substances that are active in this so-called tetrad model are consideredto have affinity for the cannabinoid receptors. It has further beenshown that cannabinoid receptor antagonists are highly effective inblocking the effects of a cannabinoid agonist in the mouse tetrad model.

The tetrad model is described, for example, in the publication of A. C.Howlett et al, International Union of Pharmacology XXVII. Classificationof Cannabinoid Receptors, Pharmacol Rev 54, 161-202, 2002 and David R.Compton et al., “In-vivo Characterization of a Specific CannabinoidReceptor Antagonist (SR141716A): Inhibition ofTetrahydroccannbinol-induced Responses and Apparent Agonist Activity”,J. Pharmacol. Exp. Ther. 277, 2, 586-594, 1996. The corresponding partsof the description are hereby incorporated by reference.

Material and Methods

Male NMRI mice with a weight of 20-30 g (Harlan, Barcelona, Spain) areused in all of the following experiments.

Before testing in the behavioural procedures given below, mice areacclimatised to the experimental setting. Pre-treatment control valuesare determined for analgesia hot plate latency (in seconds), rectaltemperature, sedation and catalepsy.

In order to determine the agonistic activity of the substance to betested, the mice are injected intravenously with the substance to betested or the vehicle alone. 15 minutes after injection, latency in hotplate analgesia is measured.

Rectal temperature, sedation and catalepsy are measured 20 minutes afterinjection.

In order to determine the antagonistic activity the identical procedureis used as for the determination of the agonistic effects, but with thedifference that the substance to be evaluated for its antagonisticactivity is injected 5 minutes before the intravenous injection of 1,25mg/kg Win-55,212 a known cannabinoid-receptor agonist.

Hot Plate Analgesia

The hot plate analgesia is determined according to the method describedin Woolfe D. et al. “The evaluation of analgesic action of pethidinehydrochloride (Demerol)”, J. Pharmacol. Exp. Ther, 80, 300-307, 1944.The respective description is hereby incorporated by reference and formspart of the present disclosure.

The mice are placed on a hot plate (Harvard Analgesimeter) at 55±0.5° C.until they show a painful sensation by licking their paws or jumping andthe time for these sensations to occur is recorded. This reading isconsidered the basal value (B). The maximum time limit the mice areallowed to remain on the hot plate in absence of any painful response is40 seconds in order to prevent skin damage. This period is called thecut-off time (PC).

Fifteen minutes after the administration of the substance to be tested,the mice are again placed on the hot plate and the afore describedprocedure is repeated. This period is called the post-treatment reading(PT).

The degree of analgesia is calculated from the formula;% MPE of Analgesia=(PT−B)/(PC−B)×100MPE=Maximum possible effect.Determination of Sedation and Ataxia

Sedation and ataxia is determined according to the method described inDesmet L. K. C, et al, “Anticonvulsive properties of Cinarizine andFlunarizine in Rats and Mice”, Arzneim.-Forsch. (Frug Res) 25, 9, 1975.The respective description is hereby incorporated by reference and formspart of the present disclosure,

The chosen scoring system is

-   0: no ataxia;-   1: doubtful;-   2: obvious calmness and quiet;-   3 pronounced ataxia;

prior to as well as after treatment.

The percentage of sedation is determined according to the formula:% of sedation arithmetic mean/3×100Hypothermia:

Hypothermia is determined according to the method described in David R.Compton et al. “In-vivo Charecterization of a Specific CannabinoidReceptor Antagonist (SR141716A) Inhibition ofTetrahydrocannbinol-induced Responses and Apparent Agonist Activity”, J.Pharmacol Exp Ther. 277, 2, 586-594, 1996. The respective description ishereby incorporated by reference and forms part of the presentdisclosure.

The base-line rectal temperatures are determined with a thermometer(Yello Springs Instruments Co., Panlabs) and a thermistor probe insertedto 25 mm before the administration of the substance to be tested. Rectaltemperature is again measured 20 minutes after the administration of thesubstances to be tested. The temperature difference is calculated foreach animal, whereby differences of >2° C. are considered to representactivity,

Catalepsy:

Catalepsy is determined according to the method described in AlpermannH. G. et al. “Pharmacological effects of Hoe 249: A new potentialantidepressant”, Drugs Dev. Res. 25, 267-282, 1992. The respectivedescription is hereby incorporated by reference and forms part of thepresent disclosure.

The cataleptic effect of the substance to be tested is evaluatedaccording to the duration of catalepsy, whereby the animals are placedhead downwards with their kinlegs upon the top of the wooden block.

The chosen scoring system is:

Catalepsy for;

more than 60 seconds=6; 50-60 seconds=5, 40-50 seconds=4, 30-40seconds=3, 20-30 seconds=2, 5-10 seconds=1, and less than 5 seconds=0.

The percentage of catalepsy is determined according to the followingformula:% Catalepsy=arithmetic mean/6×100III. In vivo Testing for Antiobesic Activitya) Accute Treatment

Normally handled rats were habituated to a reversed cycle 12/12h, andthe tested compound as well as saline was acutely orally administered.After administration the cumulated food intake (g) was measured at 6 hand 24 h. Following that the difference in body weight between controland compound treated animals was measured. This is a variation of thetest according to Colombo et al. as described below.

b) Long-Term Treatment

The in-vivo testing for antiobesic activity of the inventive pyrazolinecompounds is carried out as described in the publication of G. Colomboet al., “Appetite Suppression and Weight Loss after the CannabinoidAntagonist SR 141716”; Life Sciences, 63 (8), 113-117, (1998). Therespective part of the description is hereby incorporated by referenceand forms part of the present disclosure.

IV. In vivo Testing for Antidepressant Activity

The in-vivo testing for antidepressant activity of the inventivepyrazoline compounds in the water despair test is carried out asdescribed in the publication of E. T. Tzavara et al., “The CB1 receptorantagonist SR141716A selectively increases monoaminergicneurotransmission in the medial prefrontal cortex: implications fortherapeutic actions”; Br. J. Pharmacol. 2003, 138(4):544:53. Therespective part of the description is hereby incorporated by referenceand forms part of the present disclosure.

V. In vitro Determination of Antagonism to CB1-Receptor

Membrane Preparation:

Chinese hamster ovary (CHO) cells stably expressing recombinant humancannabinoid 1 receptor (CB1) were cultured in nutrient mixture Ham's F12 supplemented with 10% heat-inactivated fetal bovine serum, 2 mML-glutamine, 50 U/ml penicillin, 50 U/ml streptomycin and 0.5 mg/mlgeneticin. In order to obtain cells, culture flasks were washed twicewith phosphate buffered saline and scraped. Then, cells were collectedby centrifugation (200×g, 10 min) and stored dry at −80° C. Cells werehomogenized in ice-cold 20 mM HEPES, 10 mM EDTA (pH 7.5) and centrifugedat 40,000×g for 15 min at 4° C. The membrane pellet was resuspended in20 mM HEPES, 0.1 mM EDTA (pH 7.5) and centrifuged for 15 min at 4° C.The final membrane pellet was resuspended in 20 mM HEPES, 0.1 mM EDTA(pH 7.5), and divided in aliquots and stored at −80° C. until use.

[³⁵S]GTPγS Binding Assay:

The reaction was performed in 96-well plates. Membranes (15 μgprotein/well) were incubated for 60 min at 30° C. in buffer (50 mMHEPES, 100 mM KCl, 5 mM MgCl₂, 1 mM EDTA, 0.1% wt/vol bovine serumalbumin, 5 μM GOP, saponin (10 μg/ml), 0.5 nM [³⁵S]GTPγS, pH 7.4) withcompound at a final concentration of 1 μM in either the absence orpresence of agonist WIN 55,212-2 between 3 nM and 3 μM. The incubationwas terminated by rapid filtration through Millipore Multiscreen glassfiber FB, and rinsed two-times with ice-cold assay buffer. Filter plateswere dried and 30 μl of scintillation liquid was added. Radioactivitywas determined using a Wallac Microbeta Trilux. Each experiment wasperformed at least in duplicate. A WIN 55,212-2 dose-response experimenteither alone or in the presence of Rimonabant (1 μM) was systematicallyperformed.

Calculations:

The average of basal [³⁵S]GTPγS binding was subtracted from all bindingdata. In order to compare the antagonism results from one screeningcampaign to another one, the difference between the maximal agonisteffect of WIN 55,212-2 alone, and the maximal antagonism effect due toWIN 55,212-2 plus Rimonabant (1 μM) was defined as 100%.

Further Methods:

Alcohol Intake

The following protocol may be used to evaluate the effects of alcoholintake in alcohol preferring (P) female rats (e.g. bred at IndianaUniversity) with an extensive drinking history. The following referenceprovides detailed a description of P rats: Lumeng, L. et al., “Differentsensitivities to ethanol in alcohol-preferring and-nonpreferring rats,”Pharmacol. Biochem Behav., 16, 125-130 (1982).

Female rats are given 2 hours of access to alcohol (10% v/v and water,2-bottle choice) daily at the onset of the dark cycle. The rats aremaintained on a reverse cycle to facilitate experimenter interactions.The animals are initially assigned to four groups equated for alcoholintakes: Group 1-vehicle; Group 2-positive control (e.g. 5.6 mg/kgAM251; Group3-low dose test compound; and Group 4-high dose of testcompound. Test compounds are generally mixed into a vehicle of 30%(w/v)—cyclodextrin in distilled water at a volume of 1-2 ml/kg. Vehicleinjections are given to all groups for the first two days of theexperiment. This is followed by 2 days of drug injections (to theappropriate groups) and a final day of vehicle injections. On the druginjection days, drugs are given sc 30 minutes prior to a 2-hour alcoholaccess period. Alcohol intake for all animals is measured during thetest period and a comparison is made between drug and vehicle-treatedanimals to determine effects of the compounds on alcohol drinkingbehavior.

Additional drinking studies can be done utilizing female C57BI/6 mice(Charles River). Several studies have shown that this strain of micewill readily consume alcohol with little to no manipulation required(Middaugh et al. “Ethanol Consumption by C57BU6 Mice: Influence ofGender and Procedural Variables” Alcohol, 17 (3),175-183, 1999, Le etal., “Alcohol Consumption by C57BL/6, BALA/c, and DBA/2 Mice in aLimited AccessParadigm” PharmacologyBiochemistry and Behavior, 47,375-378, 1994).

For example, upon arrival mice are individually housed and givenunlimited access to powdered rat chow, water and a 10% (w/v) alcoholsolution. After 2-3 weeks of unlimited access, water is restricted for20 hours and alcohol is restricted to only 2 hours access daily. This isdone in a manner that the access period was the last 2 hours of the darkpart of the light cycle.

Once drinking behavior is stabilized, testing can commence. Mice areconsidered stable when the average alcohol consumption for 3 days is 20%of the average for all 3 days. Day 1 of test consists of all micereceiving vehicle injection (sc or ip). Thirty to 120 minutes postinjection access is given to alcohol and water. Alcohol consumption forthat day is calculated (g/kg) and groups are assigned so that all groupshave equivocal alcohol intake. On day 2 and 3, mice are injected withvehicle or drug and the same protocol as the previous day is followed.Day 4 iss wash out and no injections are given. Data is analyzed usingrepeated measures ANOVA. Change in water or alcohol consumption iscompared back to vehicle for each day of the test. Positive resultswould be interpreted as a compound that was able to significantly reducealcohol consumption while having no effect on water

Oxygen Consumption Methods:

Whole body oxygen consumption is measured using an indirect calorimeter(Oxymax from Columbus Instruments, Columbus, Ohio) in male SpragueDawley rats (if another rat strain or female rats are used, it will bespecified). Rats (e.g. 300-380 g body weight) are placed in thecalorimeter chambers and the chambers are placed in activity monitors.These studies are done during the light cycle. Prior to the measurementof oxygen consumption, the rats are fed standard chow ad libitum. Duringthe measurement of oxygen consumption, food is not available. Basalpre-dose oxygen consumption and ambulatory activity are measured every10 minutes for 2.5 to 3 hours. At the end of the basal pre-dosingperiod, the chambers are opened and the animals are administered asingle dose of compound (the usual dose range is 0.001 to 10 mg/kg) byoral gavage (or other route of administration as specified, i.e., sc,ip, iv). Drugs are prepared in methylcellulose, water or other specifiedvehicle (examples include PEG400, 30% beta-cyclo dextran and propyleneglycol). Oxygen consumption and ambulatory activity are measured every10 minutes for an additional 1-6 hours post-dosing.

The Oxymax calorimeter software calculates the oxygen consumption(ml/kg/h) based on the flow rate of air through the chambers anddifference in oxygen content at inlet and output ports. The activitymonitors have 15 infrared light beams spaced one inch apart on eachaxis, ambulatory activity is recorded when two consecutive beams arebroken and the results are recorded as counts.

Resting oxygen consumption, during pre- and post-dosing, is calculatedby averaging the 10-min02 consumption values, excluding periods of highambulatory activity (ambulatory activity count>100) and excluding thefirst 5 values of the pre-dose period and the first value from thepost-dose period. Change in oxygen consumption is reported as percentand is calculated by dividing the post-dosing resting oxygen consumptionby the pre-dose oxygen consumption *100. Experiments will typically bedone with n=4-6 rats and results reported are mean±SEM.

Interpretation:

An increase in oxygen consumption of >10% is considered a positiveresult. Historically, vehicle-treated rats have no change in oxygenconsumption from pre-dose bassal.

Nicotine Dependence

An intravenous nicotine self-administration model or place preferencemodel may be used to assess the effects of a test compound on nicotinedependence (see, e.g., Vastola, et al. Physiol. Behav. 77:107-114, 2002;Brower, et al., Brain Res. 930:12-20, 2002).

Place Preference

Sprague-Dawley rats are used in this study (Vastola, et al., 2002).Animals are housed in a temperature-controlled, 12h/12h illuminationcycle with ad libitum access to food and water. Conditioning and testingare conducted in a chamber divided into two compartments with a doorseparating the two compartments. Behavior of the animals is recorded byvideo camera.

Animals are habituated to the injection procedure for several days. Theanimals are then placed into the test chamber and given free access toboth compartments. The initial preference for a particular compartmentis determined. For the conditioning trials, animals are injected withnicotine and restricted to the nonpreferred compartment, or the animalsare injected with saline and restricted to the preferred compartment. Ontest day, the door separating the compartments is removed, the animal isplaced in the center of the chamber and allowed to move freely betweencompartments. Time spent in each compartment is scored. Preferentialoccupancy of the nicotine compartment follows from the conditionedreinforcing effects of nicotine.

Self-Administration

Self-administration in animals is a predictor of a compound's abusepotential in humans. Modifications to this procedure may also be used toidentify compounds that prevent or block the reinforcing properties ofdrags that have abuse potential. A compound that extinguishes theself-administration of a drag may prevent that drag's abuse or itsdependence.

Sprague-Dawley rats are used in this study. Initially, animals arehoused in a temperature-controlled, 12 h/12 h illumination cycle with adlibitum access to food and water. The animals are then implanted withjugular catheters which exit through the animal's back, and each animalis placed in an individual operant chamber (Brower, et al., 2002). Thecatheters are connected to a computer-driven syringe pump which islocated outside of the chamber. The chamber contains two levers with agreen light located above each lever. The light is illuminated whennicotine is available.

In a self-administration test, animals are placed in the operantchambers and the levers are randomly designated as an active andinactive lever. Each response on the active lever produces an infusionof nicotine. Presses on the inactive lever have no effect, but are alsorecorded. Animals are then trained to self-administer nicotine over aset period of time by having drag access during each daily session.Illumination of the chamber house light signals the beginning of thesession and the availability of nicotine. When the session ends, thehouse light is turned off. Initially, a nicotine infusion occurs withevery press of the active lever. Once lever-pressing behavior has beenestablished, the number of presses to produce a nicotine infusion isincreased. After stable nicotine self-administration is obtained, theeffect of a test compound on the nicotine-reinforced behavior may beevaluated. Administration of this test compound prior to the session caneither potentiate, extinguish, or produce no change to theself-administrating behavior. Tests are conducted every two days, andthe order of the administration of the test compound doses iscontrolled.

Alzheimer/Dementia Experiments

Morris Water Maze Task

The Morris water maze is a behavioral in vivo test to measure spatialorientation learning and memory through a complex learning task. It ishighly suitable for testing compounds that enhance learning and memory.A circular water tank or pool (diameter 2 m, height 0.7 m) is filledwith water, and a 10 cm2 platform is placed 1-1.5 cm below the watersurface at a defined location within the pool. The escape platform isnot visible for an animal swimming in the water tank. For theexperiment, a rat or mouse is placed into the pool to swim freely.

The animals have the task to localize the submerged platform, and thetime and distance required for successful retrieval is measured.Multiple extra-maze cues are provided by the furniture in the room,including desks, computer equipment, a second water tank, the presenceof the experimenter, and by a radio on a shelf that is playing softly.

Before administration of the test compound, animals are usually trainedin the task 4 times a day for 5 days. Test compounds are administeredorally or intraperitoneally on the day of the experiment at a definedtime (e.g., 30 minutes before the first swim test). Control animals aredosed with the corresponding vehicle not containing test compound.Active compounds yield shorter times and distances to localize theplatform (i.e., the better the animal remembers the location of theplatform, the shorter the distance covered and the faster the platformis reached).

The test can also be carried out using transgenic or cognitivelyimpaired animals. Cognitive impairment is induced either by old age orexperimentally through brain lesions, such as bilateral lesions of theentorhinal cortex in rats. Such lesions can be induced by intracerebralinjections of the excitotoxin ibotenic acid.

Object Recognition Task

The object recognition task is used to assess the effects of compoundson the cognitive performance of rodents. A rat is placed in an openfield, in which two identical objects are located. The rats inspectsboth objects during the initial trial of the test. After a certainretention interval (e.g., 24 hours), a second trial is carried out.Here, one of the two objects used in the first trial (the ‘familiar’object) and a novel object are placed in the open field, and theinspection time at each of the objects is measured. Good retention isreflected by higher exploration times towards the novel compared withthe ‘familiar’ object.

Administration of the putative cognition enhancer prior to the firsttrial predominantly allows assessment of the effects on acquisition, andon the consolidation processes. Administration of the test compoundafter the first trial allows to assess the effects on consolidationprocesses, whereas administration before the second trial allows tomeasure effects on retrieval processes.

Passive Avoidance Task

The passive avoidance task assesses memory performance in rats and mice.The inhibitory avoidance uses an apparatus consisting of a box with twocompartments separated by a guillotine door that can be operated by theexperimenter. One compartment is illuminated with bright light, and theother compartment is dark. A threshold of 2 cm separates the twocompartments when the guillotine door is 15 raised. When the door isopen, the illumination in the dark compartment is about 2 lux. The lightintensity is about 500 lux at the center of the floor of the lightcompartment.

Two habituation sessions, one shock session, and a retention session aregiven, separated by inter-session intervals of 24 hours. During thehabituation sessions and the retention session, the rat is allowed toexplore the apparatus for 300 seconds.

The rat is placed in the light compartment, facing the wall opposite tothe guillotine door. After an accommodation period of 15 seconds, theguillotine door is opened so that all parts of the apparatus can bevisited freely. Rats normally avoid brightly lit areas and will enterthe dark compartment within a few seconds.

In the shock session, the guillotine door between the compartments islowered as soon as the rat has entered the dark compartment with allpaws, and a scrambled 1 mA footshock is administered for 2 seconds. Thenthe rat is removed from the apparatus and returned into its home cage.The procedure during the retention session is identical to that of thehabituation sessions.

The step-through latency, that is, the first latency of entering thedark compartment (in seconds) during the retention session is an indexof the memory performance of the animal: a better retention is assumedif the latency to enter the dark compartment is longer. A test compoundis given 30 minutes before the shock session, together with 1 mg/kgscopolamine. Scopolamine impairs the memory performance during theretention session 24 hours later. If the test compound increases theenter latency compared with the scopolamine-treated controls, it isconsidered to possess cognition enhancing activity. T-maze SpontaneousAlternation Task

The T-maze spontaneous alternation task (TeMCAT) assesses the spatialmemory performance in mice. The start arm and the two goal arms of theT-maze are provided with guillotine doors that can be operated manuallyby the experimenter. A mouse is put into the start arm at the beginningof training. In the first trial, either the left or right goal arm isblocked by lowering the respective guillotine door (forced trial).

After the mouse has been released from the start arm, it will explorethe maze, eventually entering the open goal arm, and return to the startposition, where it will be confined for 5 seconds, by lowering theguillotine door. Then, the animal can choose freely between the left andright goal arm (all guillotine-doors opened) during 14 additional trials(free choice trials). As soon as a mouse has entered one goal arm, theother arm is closed. The mouse eventually returns to the start arm andis free to visit whichever arm it wants after having been confined tothe start arm for 5 seconds.

After completion of 14 free choice trials in one session, the animal isremoved from the maze,

Out of the 14 trials the alternations in percent are calculated. Thispercentage and the total time needed to complete the first forced trialand the subsequent 14 free choice trials (in seconds) is analyzed. Inaddition, cognitive deficits can be induced by injection of scopolamine30 minutes before the start of the training session. A cognitionenhancer, administered before the training session, will at leastpartially, antagonize the scopolamine-induced reduction in thespontaneous alternation rate.

Depression Model

A forced swim or tail suspension model may be used to assess theefficacy of antidepressant compounds (see, e.g., Porsolt, et al., Nature266:730-732, 1977; Stem, et al., Psychopharmacology 85:367-370, 1985).

Forced Swim Test

Rats or mice are placed in a cylinder filled with water 23-25° C. fromwhich no escape is possible. Initially, animals struggle and try toescape, but eventually adopt a characteristic immobile posture and makeno further attempts to escape except for small movements needed theirhead above water. Animals are dosed with a compound and the activity(swimming or climbing) or immobility is measured by an observer. Theimmobility is considered by some to reflect a ‘behavioral despair’ inwhich animals cease to struggle to escape the aversive situation. A widevariety of clinically used antidepressants (TCAs, MAOIs, SSRIs,atypicals) decrease immobility in this test and has a good predictivevalidity in that it detects antidepressants with different mechanisms ofaction but its construct validity is weak. At least two distinct activebehavioral patterns are produced by pharmacologically selectiveantidepressant drugs. Serotonin-selective reuptake inhibitors increaseswimming behavior, whereas drugs acting primarily to increaseextracellular levels of norepinephrine or dopamine increase climbingbehavior. There are false positives (psychostimulants) but relativelyfew false negatives ([beta]-adrenergic agonists). The test is sensitiveto muscle-relaxant (benzodiazepines) and sedative (neuroleptics)effects, leading to enhanced immobility. False positives and falsenegatives can often be screened by measuring if the compound produceslocomotor stimulation or sedation.

Tail Suspension Test

When suspended by the tail, mice will initially struggle and try toescape and then alternate between active escape attempts andimmobililty. In this test, animals are dosed with a compound and theimmobility is measured by an observer for 6 min. Porsolt describes theimmobile behavior as ‘behavioral despair’ which animals cease tostruggle to escape the aversive situation. A large variety of clinicallyantidepressants (tricyclics, MAOIs, SSRIs, and atypicals) reduceimmobility in this model. The test has a good predictive validity forantidepressant activity and works for most antidepressant classesincluding but has some false positives (psychostimulants). The test issensitive to muscle-relaxant (benzodiazepines) and sedative(neuroleptics) effects, which lead to enhanced immobility. Falsepositives and false negatives can often be screened by measuring if thecompound produces locomotor stimulation or sedation. Strain differencesin the tail suspension test have been found in mice. The tail suspensiontest has some face validity but its construct validity is rather weak.

Schizophrenia Model

A prepulse inhibition model may be used to assess the efficacy ofantipsychotic compounds (see Swerdlow and Geyer, Schizophrenia Bulletin24; 285-301, 1998).

Prepulse Inhibition

Prepulse inhibition is the process whereby a relatively mild stimulus,the prepulse, suppresses the response to a strong, startle-elicitingstimulus when the prepulse precedes the startle stimulus by a briefduration (about 10 to 500 milliseconds). Prepulse inhibition is across-species phenomenon (ie, it is present in mammals ranging from miceto humans), yet it is relatively absent among schizophrenic patients.The deficit in PPI in schizophrenic patients is thought to reflect theloss of sensorimotor gating that may lead to sensory flooding andcognitive fragmentation. In this test, mice or rats are administeredcompounds and individually placed into a holder on a transducer platformto measure whole body startle. The holder is housed in a startle chamberwith background white noise. Following a brief habituation period,animals are given multiple trials of a weak auditory prepulse stimululs,followed by a strong auditory startle stimulus. Four types of trials aregiven: prepulse plus startle, prepulse alone, startle alone, and nostimulation. PPI is measured as the amount of inhibition of startlefollowing the prepulse and is expressed as the percentage of basicstartle. As a control, measurements are taken in the no stimulation andprepulse alone trials. PPI is considered a test with good predictive,face and construct validity for schizophrenia. Putative antipsychoticscan be tested alone to determine if they enhance PPI. Alternately,antipsychotics can be screened to determine if they block various agentsthat disrupt PPI (apomorphine, d-amphetamine, PCP, ketamine, DOI).Finally, mutant mice with or without drugs can be screened using the PPIprocedure.

Anxiety Model

An elevated plus maze model may be used to assess the efficacy ofanxiolytic compounds (see Pellow and File, Pharm. Biochem. Behav. 24,525-529, 1986).

Elevated Plus Maze

The elevated plus maze is widely used as an anxiety paradigm thatexamines the conflict between the drive to explore and the aversivenessof heights and open spaces of rats or mice. The maze is a cross made upof two open and two closed arms that is raised above the ground. Thecombination of light, the open arms, and the height is thought toproduce unconditioned fear or anxiety responses in mice or rats. Thetest apparatus is an open top maze constructed of opaque plastic withalternating open and enclosed arms. For rats, each arm is 45-55 cm longand 8-12 cm wide, with the sides of the enclosed arms 35-45 cm high, thejuncture approximately 10×10 cm, and the maze is elevated 45-55 cm abovethe floor. The mouse elevated plus maze consists of two closed arms(15×6×30 cm) and two open arms (1×6×30 cm) forming a cross, with aquadrangular center (6×6 cm). The maze is placed 50 cm above the floor.Testing is performed in a room free of noise and distraction. On testdays animals are administered drug or vehicle. If a pretreatment periodis necessary, the animals are returned to the home cage for the durationof the pretreatment time; otherwise, the animals are placed in a clearplastic holding chamber singly or with cage mates for 1-10 minutes priorto test time. Rats are then placed in the center of the maze alwaysoriented in the same direction, either consistently facing an open armor an enclosed arm. For 5-10 minutes, entries into each arm and the timespent in each arm are recorded by the observer(s) or by videotape or acomputer receiving input from a video camera mounted above the maze. Tocount as an entry, all four paws must be inside the arm. If necessary,additional measures of anxiety-related behaviors will be recorded, i.e.,time spent motionless, time spent in the center, time spent grooming,and the number of rears, stretching postures or feces produced.Following testing the animals are returned to the home cages. Whenanimals are placed in the center of the maze, they spend most of theirtime in the closed arms, avoiding the open arms. Anxiolytic drugs, suchas benzodiazepines, will increase the amount of time animals spend inthe open arms. The test is also sensitive to anxiogenic drugs, whichfends strong support for its predictive validity.

Erectile Dysfunction

Drugs affecting erectile function may be tested by measuring the effecton apomorphine-evoked increases in intracavernous pressure in the awakerat as described by Andersson, et al., (J. Urol. 161: 1707-17] 2, 1999).One end of a polyethylene tubing is implanted into the cavernosal spaceof the penis of male Sprague-Dawley rats. After recovery from thesurgery, intracavernous pressure is recorded using a pressure transducerconnected to a multichannel pen-recorder. Erections are induced byadministration of apomorphine (100-250 ug/kg s.c.) with or without testcompound, and the results are compared for the treated group and thenon-treated group.

Female Sexual Dysfunction

Systems to test compounds for the treatment of female sexual dysfunctioninclude in vitro and in situ models using vaginal or clitoral smoothmuscle preparations, histological evaluation, and vaginal blood flowassessments. In vivo studies of sexual responses focus on behavioralparadigms involving lordotic posturing and receptivity, as well asindices of motivation using a dual chamber pacing method (see, e.g.,Hale, et al., Int. J. Impot. Res. 15 Suppl 5: S75-79, 2003).

The present invention is illustrated below with the aid of examples.These illustrations are given solely by way of example and do not limitthe general spirit of the present invention.

EXAMPLES Preparation of 4-(4-chlorophenyl)-2-oxo-3-butenoic acid

p-Chlorobenzaldehyde (13.3 g, 95 mmol) and ethyl pyruvate (10 g, 86mmol) were dissolved in 150 mL of absolute ethanol. The solution wascooled to 0° C. and an aqueous solution of NaOH (3.8 g in 45 mL water)was added drop wise keeping the temperature below or equal to 10° C.,whereby a yellow-orange coloured precipitate was formed. The reactionmixture was stirred for 1 hour at 0° C. and an additional 1.5 hours atroom temperature (approximately 25° C.). Afterwards the reaction mixturewas cooled down to approximately 5° C. and the insoluble sodium salt of4-(4-chlorophenyl)-2-oxo-3-butenoic acid was isolated by filtration.

The filtrate was left in the refrigerator overnight, whereby moreprecipitate was formed, which was filtered off, combined with the firstfraction of the salt and washed with diethyl ether. The sodium salt of4-(4-chlorophenyl)-2oxo-3-butenoic acid was then treated with a solutionof 2N HCl, stirred for some minutes and solid4-(4-chlorophenyl)-2-oxo-3-butenoic acid was separated via filtrationand dried to give 12.7 g of the desired product (70% of theoreticalyield).

IR (KBr, cm⁻¹): 3500-2500, 1719.3, 1686.5, 1603.4, 1587.8, 1081.9.

¹H NMR(CDCl₃, 300 MHz) δ 7.4 (d, J=8.4 Hz, 2H), 7.5 (d, J=16.1 Hz, 1H),7.6 (d, J=8.4 Hz, 2H), 8.1 (d, J=16.1 Hz, 1H).

Preparation of5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid

4-(4-Chlorophenyl)-2-oxo-3-butenoic acid (12.6 g, 60 mmol),2,4-dichlorophenylhydrazine hydrochloride (12.8 g, 60 mmol) and glacialacetic acid (200 mL) were mixed under a nitrogen atmosphere and heatedto reflux for 4 hours, cooled down to room temperature (approximately25° C.) and poured into ice, whereby a sticky mass was obtained, whichwas extracted with methylene chloride. The combined methylene chloridefractions were washed with water, dried over sodium sulfate, filteredand evaporated to dryness to give a pale yellow solid (12.7 g, 57% oftheoreticat yield).

IR (KBr, cm⁻¹): 3200-2200, 1668.4, 1458, 1251.4, 1104.8.

¹H NMR (CDCl₃, 300 MHz) δ 3.3 (dd, 1H), 3.7 (dd, 1H), 5.9 (dd, 1H),7.09-7.25 (m, 7H)

Preparation of5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid chloride

5-(4-Chlorophenyl-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid (5.54 g, 15 mmols) was dissolved in 120 mL of dry toluene andthionyl chloride (2.14 g, 18 mmol) was added. The mixture was heated to80° C. for 2.5 hours. The solvent was removed under reduced pressure andthe resulting crude residue (6.06 g, 100%) was used without any furtherpurification.

IR (KBr, cm⁻¹): 1732, 1700, 1533, 1478, 1212, 826

Example 1 Preparation of5-(4Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid piperidin-1-ylamide

N-Aminopiperidine (0.6 mL, 5.6 mmol) and triethylamine (4 mL) weredissolved in methylene chloride (25 mL) under nitrogen atmosphere. Theresulting mixture was cooled to 0° C. and a solution of5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid chloride in methylene chloride (15 mL) was added drop wise. Theresulting reaction mixture was stirred at room temperature(approximately 25° C.) overnight. The reaction mixture was washed withwater, followed by a saturated aqueous solution of sodium bicarbonate,again with water, dried over sodium sulfate, filtered and evaporated todryness in a rotavapor. The resulting crude solid was crystallised fromethanol. The crystallised solid was removed via filtration and themother liquors were concentrated to yield a second fraction ofcrystallised product. The two fractions were combined to give a totalamount of 1.7 g (57% of theoretical yield) of the title compound havinga melting point of 183-186° C.

IR (KBr, cm⁻¹): 3222.9, 2934.9, 1647.4, 1474.7, 1268.3, 815.6.

¹H NMR (CDCl₃, δ): 1.4 (m, 2H), 1.7 (m, 4H), 2.8 (m, 4H), 3.3 (dd, J=6.1y 18.3 Hz, 1H), 3.7 (dd. J=12.5 and 18.3 Hz, 1H), 5.7 (dd, J=6.1 and12.5 Hz, 1H), 7.0-7.2 (m, 6H), 7.4 (s, 1H).

The following compounds were prepared according to the processesdescribed for the preparation of compound 1 above. Those skilled in theart are familiar with the starting materials that are needed to obtainsaid compounds.

Example 7 N-oxide ofN-piperidinyl-5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4,5-dihydropyrazole-3-carboxamide

Under nitrogen gas as an inert atmosphereN-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydropyrazole-3-carboxamide(0.15 g, 0.33 mmol) was dissolved in 7 mL of dichloromethane. Theresulting solution was ice-cooled to 0° C. and m-chloroperbenzoic acid(0.204 g, 0.83 mmol) was added in several portions. After stirring for15 minutes a control via thin layer chromatography showed that nostarting material was present. A saturated solution of sodiumbicarbonate was then slowly added, the organic phase separated, washedwith water, dried over sodium sulfate and filtered. The filteredsolution was evaporated to dryness and the crude product was purifiedvia column chromatography yielding 78 mg (50% of theoretical yield) ofthe N-oxide ofN-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydropyrazole-3-carboxamidein form of a white solid having a melting point of 115-120° C.

IR (KBr, cm⁻¹): 3202, 1678, 1654, 1474, 1309, 1107.

¹H-NMR (CDCl₃, δ): 1.6 (m, 2H), 1.8-2.0 (m, 4H), 2.55 (m, 2H), 3.3 (dd,J=6.3 Hz and 18.2 Hz, 1H), 3.7 (m, 3H), 5.8 (dd, J=6.3 Hz and 12.5 Hz,1H), 7.0-7.3 (m, 7H), 8.5 (s, 1H.)

Example 120[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-carboxylicacid ethyl ester

5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid (0.55 g, 1.50 mmol) was dissolved in 20 mL of toluene and (2 mL)ethanol and (0.05 g) of p-toluenesulfonic acid monohydrate were added.The mixture was heated at 80° C. for 72 hours. After cooling to roomtemperature, the reaction mixture washed with sodium hydrogen carbonatesolution and water, dried over sodium sulphate and evaporated to drynessto give the title compound in form of oil.

IR (film, cm⁻¹): 2981, 1728, 1704, 1478, 1246.

The compounds according to the following examples 68 to 172 have beenprepared by the methods described for the preparation of Example 1. Theother examples were prepared or can be prepared by the methods describedabove.

Example 685-(4Bromo-phenyl)-1-(2,4dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide Preparation of 4-(4-bromophenyl)-2-oxo-3-butenoicacid

This compound was obtained following the same method described inExample 1 starting from p-bromobenzaldehyde.

¹H NMR (400 MHz, CDCl₃,): δ7.55 (2H, m, ArH,), 7.61 (3H, m, Ar H), 8.09(1H, d, J 16.4 Hz)

¹³C NMR (100 MHz, CDCl₃): δ 118.1 (CH), 127.2 (C), 130.7 (CH), 132.7(CH), 149.7 (C+CH), 160.0 (CO), 182.2 (CO).

Preparation of5-(4bromophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid

IR (KBr, cm⁻¹): 3200-2200, 1685, 1571, 1549, 1480, 1112

¹H NMR (400 MHz, CDCl₃)): δ3.27 (1H, dd, J 18.0, 6.4 Hz, ArH,), 3.71(1H, dd, J 18, 12.8 Hz, Ar H), 5.88 (1H, dd, J 12.8, 6.4 Hz, CH), 7.02(2H, d, J 7.6 Hz, ArH), 7.08 (1H, m, ArH), 7.19 (1H, d J 8.4 Hz, ArH),7.26 (1H, m, ArH), 7.37 (2H, d, 7.6 Hz, ArH)

¹³C NMR (100 MHz, CDCl₃): δ 40.4 (CH₂), 67.4 (CH), 122.7 (C), 126.0(CH), 126.5 (C), 127.6 (CH), 128.3 (CH), 130.2 (CH), 131.2 (C), 132.2(CH), 138.4 (C), 138.5 (C), 140.2(C), 165.7(C).

Preparation of5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid chloride

IR (KBr, cm⁻¹): 1737, 1534, 1477, 1212, 1127.

Preparation of5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide

This compound was obtained following the same method described inExample 1 starting from5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid chloride and azepan-1-amine.

¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.75 (br. s., 4 H) 2.00 (br. s., 4H) 3.26 (dd, J=18.16, 6.15 Hz, 1 H) 3.71 (dd, J=18.16, 12.45 Hz, 1 H)3.65 (br. s., 4 H) 5.82 (dd, J=12.45, 6.15 Hz, 1 H) 6.97 (d, J=8.35 Hz,2 H) 7.10 (d, J=2.20 Hz, 1 H) 7.16-7.22 (m, 1 H) 7.24 (d, J=2.20 Hz, 1H) 7.35 (d, J=8.50 Hz, 2 H)

MS (M+H)⁺: 510

Example 961-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide Preparation of 4-(4-fluorophenyl)-2-oxo-3-butenoicacid

¹H NMR (400 MHz, CDCl₃): δ 7.15 (2H, apt, J 8.4 Hz, ArH,), 7.53 (1H, d,J 16.0 Hz, CH), 7.70 (2H, m, ArH), 8.11(1H, d, J 16.0 Hz)

¹³C NMR (100 MHz, CDCl₃): δ 116.5 (CH, d, J_(F) 24 Hz), 117.4 (CH, d,J_(F) 8.7 Hz), 130.1 (C, d, J_(F) 2.4 Hz), 131.7 (CH, d, J_(F) 9.1 Hz),149.9 (CH), 162.0 (C, d, J_(F) 320 Hz), 166.7 (CO), 182.4 (CO).

Preparation of5-(4-fluorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid

IR (KBr, cm⁻¹): 3200-2200, 1687.5, 1478, 1230, 1107

¹H NMR (400 MHz, CDCl₃): δ 3.30 (1H, dd, J 18.0, 6.4 Hz, ArH,), 3.72(1H, dd, J 18, 12.8 Hz, Ar H), 5.93 (1H, dd, J 12.8, 6.4 Hz, CH), 6.92(2H, t, J 8.4 Hz, ArH). 7.09-7.12 (3H, m, ArH), 7.22 (1H, bs, ArH), 7.26(1H, m, ArH)

¹³C NMR (100 MHz, CDCl₃): δ 40.7 (CH₂), 67.8 (CH), 115.9 (CH, d, J_(F)21 Hz), 126.1 (CH), 126.5 (C), 127.6 (CH), 128.3 (CH, d, J_(F) 8.2 Hz),130.1 (CH), 131.2 (C), 135.1 (C, d, J_(F) 3 Hz ), 138.6 (C), 140.1 (C),160.6 (C, d, J_(F) 240 Hz), 166.3 (C).

Preparation of5-(4-fluorophenyl)-1-(2,4dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid chloride

IR (KBr, cm⁻¹): 1733, 1548, 1511, 1478, 1212, 832.

Preparation of1-(2,4-Dichloro-phenyl)-5-(4fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide

1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.75 (br. s., 4 H) 2.00 (br. s., 4H) 3.28 (dd, J=18.16, 6.08 Hz, 1 H) 3.68 (dd, J=18.16, 12.38 Hz, 1 H)3.68 (br s., 4 H) 5.84 (dd, J=12.38, 6.08 Hz, 1 H) 6.90 (t, J=8.57 Hz, 2H) 7.08 (m, 3 H) 7.14-7.19 (m, 1 H) 7.24 (d, J=2.20 Hz, 1 H)

MS (M+H)⁺: 449

Example 1061-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid piperidin-1-ylamide hydrochloride Preparation of4-(4-methoxyphenyl)-2-oxo-3-butenoic acid

¹H NMR (400 MHz, CDCl₃): δ 3.88 (3H, s, OCH₃), 6.95 (2H, d, J 6.8 Hz),7.45 (2H, d, J 15.6 H), 7.65 (2H, d, J 6.8 Hz), 8.09 (2H, d, J 15.6 Hz).

Preparation of5-(4-methoxyphenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid

IR (KBr, cm⁻¹) 3200-2200, 1685, 1513, 1478, 1248, 1105

¹H NMR (400 MHz, CDCl₃); δ 1.45 (2H, m, CH₂), 1.75 (4H, m), 2.84 (4H,m), 3.45 (1H, dd J 4.8, 18 Hz), 3.61 (1H, dd J 11.2, 19.6 Hz), 5.93 (1H,dd J 4.8, 11.2 Hz), 6.57 (2H, ap s), 7.13 (2H, m), 7.32 (1H, m), 7.40(1H, m)

¹³C NMR (100 MHz, CDCl₃): δ 23.4 (CH₂), 25.3 (CH₂), 40.5 (CH₂), 57.3(CH₂), 63.7 (CH), 125.7 (CH), 125.8 (CH), 126.1 (CH), 127.1 (C), 127.8(CH), 130.1 (CH), 131.1 (C), 139.6 (C), 139.9 (C), 146.1 (C), 158.9(CO).

Preparation of5-(4-methoxyphenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylicacid chloride

IR (KBr, cm⁻¹): 1735, 1513, 1477 1249, 1129

Preparation of1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid piperidin-1-ylamide hydrochloride

¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.67 (br. s., 2 H) 2.10 (br. s., 4H) 3.25 (dd, J=18.02, 6.01 Hz, 1 H) 3.64 (dd, J=18.02, 12.60 Hz, 1 H)3.72 (s, 3 H) 3.89 (br. s., 4 H) 5.85 (dd, J=12.60, 6.01 Hz, 1 H) 6.72(d, J=8.79 Hz, 2 H) 7.00 (d, J=8.64 Hz, 2 H) 7.07 (dd, J=8.64, 2.20 Hz,1 H) 7.22 (d, J=8.64 Hz, 1 H) 7.22 (d, J=2.20 Hz, 1 H) 9.63 (br. s., 1H)

MS (M+H)⁺: 447

Example 1091-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid(hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride

¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.61-1.91 (m, 6 H) 2.96 (br. s., 2H) 3.27 (dd, J=18.09, 5.86 Hz, 1 H) 3.49 (m, 2 H) 3.64 (dd, J=18.09,12.60 Hz, 1 H) 3.72 (s, 3 H) 3.90 (br. s., 2 H) 5.82 (dd, J=12.60, 5.86Hz, 1 H) 6.71 (d, J=8.64 Hz, 2 H) 7.00 (d, J=8.64 Hz, 2 H) 7.06 (dd,J=8.72, 2.27 Hz, 1 H) 7.21 (m, 2 H) 9.25 (br. s., 1 H)

MS (M+H)⁺: 473

Example 1721-(2,4Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid piperidin-1-ylamide hydrochloride

The free base of compound 106 (0.82 mmol) was dissolved indichloromethane (10 ml) and a solution of 1 M BBr₃ (5 eq) indichloromethane was slowly added at 0° C. and the reation mixture wasstirred at room temperature for 8 h. The solid formed was filtered offand the solvent was evaporated. A solution of 2 N HCl in diethyl etherwas added to form the hydrochloride.

¹H NMR (300 MHz, METHANOL-d₄) δ ppm 1.69 (br. s., 2 H) 2.00 (br. s., 4H) 3.24 (dd, J=17.94, 6.23 H,z, 1 H) 3.55 (br. s., 4 H) 3.69 (dd,J=17.94, 12.38 Hz, 1 H) 5.86 (dd, J=12.38, 6.23 Hz, 1 H) 6.61 (d, J=8.50Hz, 2 H) 7.00 (d, J=8.50 Hz, 2 H) 7.17 (dd, J=8.64, 2.20 Hz, 1 H)7.26-7.38 (m, 2 H)

MS (M+H)⁺: 433

Example 1741-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid(hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride

The free base of compound 109 (0.82 mmol) was dissolved indichloromethane (10 ml) and a solution of 1 M BBr₃ (5 eq) indichloromethane was slowly added at 0° C. and the reation mixture wasstirred at room temperature for 8 h. The solid formed was filtered offand the solvent was evaporated. A solution of 2 N HCl in diethyl etherwas added to form the hydrochloride.

1H NMR (300 MHz, METHANOL-d₄) δ ppm 1.68 (br. s., 2 H) 1.81 (br. s., 4H) 2.98 (br. s., 2 H) 3.06-3.21 (m, 2 H) 3.26 (dd, J=18.02, 6.30 Hz, 1H) 3.71 (dd, J=18.02, 12.45 Hz, 1 H) 4.06 (m, 2 H) 5.88 (dd, J=12.45,6.30 Hz, 1 H) 6.63 (d, J=8.64 Hz, 2 H) 7.02 (d, J=8.64 Hz, 2 H) 7.18(dd, J=8.64, 2.34 Hz, 1 H) 7.37 (d, J=2.20 Hz, 1 H) 7.34 (d, J=8.79 Hz,1 H)

MS (M+H)⁺: 459

N⁰ STRUCTURE Name ¹H-NMR MS (M + H)⁺ 7

N-oxide of 5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl-4,5-dihydro-1H-pyrazole-3- carboxylic acid piperidin-1-ylamide 1HNMR (300 MHz, CHLOROFORM-d₆) δ ppm 1.6 (m, 2 H) 1.8–2.0 (m, 4 H) 2.55(m, 2 H) 3.3 (dd, J=18.2, 6.3 Hz, 1 H) 3.7 (m, 3 H) 5.8 (dd, J=125, 6.3Hz, 1 H) 7.0–7.3 (m, 7 H) 8.5 (s, 1 H). 8

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 1H NMR (300 MHz, CHLOROFORM-d₆) δppm 3.00 (m, 4 H) 3.32 (dd, J=18.31, 6.30 Hz, 1 H) 3.69 (dd, J=18.31,12.30 Hz, 1 H) 3.90 (m, 4 H) 5.75 (dd, J=12.30, 6.30 Hz, 1 H) 7.07 (m, 4H) 7.17 (m, 3 H) 7.68 (s,1 H) 453 9

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide hydrochloride 453 10

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro-cyclopen ta[c]pyrrol-2-yl)-amide 1H NMR (400MHz, CHLOROFORM-d₆) δ ppm 1.61 (m, 6 H) 2.77 (m, 4 H) 3.31 (dd, J=18.17,6.06 Hz, 1 H) 3.47 (s, 2 H) 3.68 (dd, J=18.17, 12.11 Hz, 1 H) 5.75 (dd,J=12.11, 6.06 Hz, 1 H) 7.05 (m, 3 H) 7.16 (t, J=8.60 Hz, 2 H) 7.25 (m, 2H) 7.75 (m, 1 H) 477 11

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid pyrrolidin-1-ylamide 1H NMR (400 MHz, CHLOROFORM-d₆) δppm 2.06 (s, 4 H) 3.28 (m, 5 H) 3.69 (dd, J=17.98, 12.50 Hz, 1 H) 5.79(dd, J=12.50, 5.86 Hz, 1 H) 7.06 (m, 3 H) 7.18 (m, 3 H) 7.25 (m, 1 H)8.22 (br, 1 H) 437 12

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,6-dimethyl-piper- idin-1-yl)-amide 1H NMR (400 MHz,CHLOROFORM-d₆) δ ppm 1.16 (m, 6 H) 1.59 (m, 2 H) 1.71 (m, 4 H) 2.39 (m,2 H) 3.35 (dd, J=18.56, 4.88 Hz, 1 H) 3.70 (dd, J=18.56, 12.50 Hz, 1 H)5.71 (dd, J=12.50, 6.06 Hz, 1 H) 6.48 (br, 1 H) 7.06 (m, 4 H) 7.18 (d,J=8.21 Hz, 2 H) 7.26 (m, 1 H) 479 13

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-methoxymethyl- pyrrolidin-1-yl)-amide 1H NMR (400MHz, CHLOROFORM-d₆) δ ppm 1.88 (m, 1 H) 2.06 (m, 2 H) 2.20 (m, 1 H) 3.30(dd, J=18.37, 5.86 Hz, 1 H) 3.37 (m, 1 H) 3.40 (s, 3 H) 3.59 (m, 2 H)3.71 (m, 3 H) 5.82 (dd, J=12.50, 5.86 Hz, 1 H) 7.05 (m, 3 H) 7.19 (d,J=8.60 Hz, 2 H) 7.24 (m, 2 H) 481 14

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-methoxymethyl- pyrrolidin-1-yl)-amide 1H NMR (400MHz, CHLOROFORM-d₆) δ ppm 1.79 (m, 1 H) 1.98 (m, 2 H) 2.13 (m, 1 H) 3.32(dd, J=18.76, 6.25 Hz, 1 H) 3.36 (m, 1 H) 3.38 (s, 3 H) 3.51 (m, 2 H)3.64 (m, 2 H) 3.70 (dd, J=18.76, 12.31 Hz, 1 H) 5.77 (dd, J=12.31, 6.25Hz, 1 H) 7.07 (d, J=8.99, 2.34 Hz, 3 H) 7.18 (d, J=8.21 Hz, 2 H) 7.24(m, 2 H) 481 15

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid [2-(1-methoxy-1- methyl-ethyl)-pyrrolidin-1-yl]-amide 1HNMR (300 MHz, DMSO-d₆) δ ppm 1.07 (m, 6 H) 1.31 (m, 3 H) 1.82 (d, J=7.03Hz, 2 H) 2.89 (m, 1 H) 3.01 (m, 1 H) 3.07 (m, 3 H) 3.18 (m, 1 H) 3.64(dd, J=18.02, 11.86 Hz, 1 H) 5.79 (m, 1 H) 7.12 (m, 2 H) 7.28 (m, 3 H)7.46 (m, 2 H) 9.33 (s, 1 H) 509 16

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azepan-1-ylamide 1H NMR (300 MHz, CHLOROFORM-d₆) δ ppm1.63 (m, 4 H) 1.80 (m, 4 H) 3.22 (dd, J=18.31, 6.15 Hz, 1 H) 3.30 (m, 4H) 3.61 (dd, J=18.31, 12.30 Hz, 1 H) 5.70 (dd, J=12.30, 6.15 Hz, 1 H)6.99 (m, 3 H) 7.10 (m, 3 H) 7.19 (m, 1 H) 465 17

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (4-methyl-cyclohexyl)- amide 464 18

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-methyl-cyclohexyl)- amide 464 19

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cycloheptylamide 1H NMR (300 MHz, DMSO-d₆) δ ppm 1.53(m, 10 H) 1.79 (m, 2 H) 3.05 (dd, J=18.16 5.71 Hz, 1 H) 3.64 (dd,J=18.16, 11.94 Hz, 1 H) 3.85 (m, 1 H) 5.80 (dd, J=11.94, 5.31 Hz, 1 H)7.13 (m, 2 H) 7.27 (m, 2 H) 7.43 (d, J=2.34 Hz, 1 H) 7.51 (d, J=8.79 Hz,1 H) 8.10 (d, J=8.35 Hz, 1 H) 464 20

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid hexylamide 1H NMR (300 MHz, DMSO-d₆) δ ppm 0.85 (m, 3 H)1.25 (m, 6 H) 1.47 (m, 2 H) 3.05 (dd, J=18.16, 5.79 Hz, 1 H) 3.17 (m, 2H) 3.65 (dd, J=18.16, 11.86 Hz, 1 H) 5.81 (dd, J=11.86, 5.79 Hz, 1 H)7.14 (d, J=8.50 Hz, 2 H) 7.27 (m, 3 H) 7.45 (m, 2 H) 8.32 (t, J=5.86 Hz,1 H) 452 21

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(4-cyclohexyl-piperazin-1-yl)- methanone 519 22

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(octahydro-isoquinolin-2-yl)- methanone 490 23

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide 1H NMR (300 MHz, CHLOROFORM-d₆) δppm 1.48 (s, 2 H) 1.84 (s, 4 H) 3.25 (s, 4 H) 3.28 (dd, J=18.16, 6.15Hz, 1 H) 3.61 (dd, J=18.16, 12.38 Hz, 1 H) 5.73 (dd, J=12.38, 6.15 Hz, 1H) 6.83, J=8.57 Hz, 2 H) 7.02 (m, 4 H) 7.18 (m, 1 H) 8.21 (br, 1 H) 43524

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (1,3-dioxo-1H,3H- benzo[de]isoquinolin-2-yl)-amide 1HNMR (300 MHz, DMSO-d₆) δ ppm 3.16 (dd, J=18.02, 6.45 Hz, 1 H) 3.79 (dd,J=18.02, 12.01 Hz, 1 H) 5.98 (dd, J=12.01, 6.45 Hz, 1 H) 7.24 (d, J=8.06Hz, 2 H) 7.36 (m, 3 H) 7.55 (m, 2 H) 7.92 (m, 2 H) 8.55 (m, 4 H) 11.08(s, 1 H) 563 25

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (1H,3H-benzo[de]iso- quinolin-2-yl)-amide 1H NMR (300MHz, DMSO-d₆) δ ppm 3.13 (dd, J=18.09, 5.86 Hz, 1 H) 3.71 (dd, J=18.09,11.86 Hz, 1 H) 4.35 (s, 4 H) 5.84 (dd, J=11.86, 5.86 Hz, 1 H) 7.19 (d,J=8.50 Hz, 2 H) 7.31 (m, 5 H) 7.47 (m, 4 H) 7.79 (d, J=8.20 Hz, 2 H)9.77 (s, 1 H) 535 26

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (4-cyclopentyl- piperazin-1-yl)-amide 520 27

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-methyl-2,3- dihydro-indol-1-yl)-amide 499 28

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,3-dihydro-indol- 1-yl)-amide 1H NMR (300 MHz,DMSO-d₆) δ ppm 2.96 (t, J=8.20 Hz, 2 H) 3.11 (dd, J=18.02, 5.71 Hz, 1 H)3.59 (t, J=8.20 Hz, 2 H) 3.73 (dd, J=18.02, 12.01 Hz, 1 H) 5.87 (dd,J=12.01, 5.71 Hz, 1 H) 6.58 (d, J=7.76 Hz, 1 H) 6.75 (t, J=7.32 Hz, 1 H)7.10 (m, 4 H) 7.29 (m, 3 H) 7.45 (d, J=2.34 Hz, 1 H) 7.54 (d, J=8.79 Hz,1 H) 10.20 (s, 1 H) 485 29

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid N′-butyl-N′-phenyl- hydrazide 1H NMR (300 MHz,CHLOROFORM-d₆) δ ppm 0.98 (t, J=7.32 Hz, 3 H) 1.45 (m, 2 H) 1.69 (m, 2H) 3.36 (dd, J=18.31, 6.84 Hz, 1 H) 3.57 (m, 2 H) 3.75 (dd, J=18.31,12.21 Hz, 1 H) 5.77 (dd, J=12.21, 6.84 Hz, 1 H) 6.90 (m, 3 H) 7.10 (m, 4H) 7.26 (m, 5 H) 8.22 (s, 1 H) 515 30

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclobutylamide 1H NMR (300 MHz, DMSO-d₆) δ ppm 1.61 (m,2 H) 2.14 (m, 4 H) 3.05 (dd, J=8.16, 5.57 Hz, 1 H) 3.63 (dd, J=18.16,11.94 Hz, 1 H) 4.33 (m, 1 H) 5.81 (dd, J=11.94, 5.57 Hz, 1 H) 7.13 (m, 2H) 7.27 (m, 3 H) 7.43 (d, J=2.34 Hz, 1 H) 7.52 (d, J=8.79 Hz, 1 H) 8.53(d, J=8.06 Hz, 1 H) 422 31

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (4-tert-butyl-cyclo- hexyl)-amide 506 32

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclohexylmethyl- amide 1H NMR (400 MHz, CHLOROFORM-d₆)δ ppm 0.99 (m, 2 H) 1.21 (m, 4 H) 1.69 (m, 1 H) 1.76 (m, 4 H) 3.15 (dd,J=17.98, 6.06 Hz, 1 H) 3.32 (dt, J=12.60, 6.40 Hz, 2 H) 3.67 (dd,J=17.98, 12.11 Hz, 1 H) 5.73 (dd, J=12.11, 6.06 Hz, 1 H) 6.75 (t, J=6.06Hz, 1 H) 7.06 (m, 3 H) 7.12 (m, 1 H) 7.17 (d, J=8.60 Hz, 2 H) 7.26 (m, 1H) 464 33

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclohexyl-ethyl- amide 478 34

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclooctylamide 1H NMR (400 MHz, CHLOROFORM-d₆) δ ppm1.59 (m, 12 H) 1.91 (m, 2 H) 3.32 (dd, J=18.37, 5.86 Hz, 1 H) 3.66 (dd,J=18.37, 12.11 Hz, 1 H) 4.10 (ddd, J=8.60, 4.01, 3.71 Hz, 1 H) 5.72 (dd,J=12.11, 5.86 Hz, 1 H) 6.65 (d, J=8.60 Hz, 1 H) 7.07 (m, 3 H) 7.15 (m, 3H) 7.25 (m, 1 H) 478 35

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (1-methyl-hexyl)- amide 1H NMR (400 MHz, CHLOROFORM-d₆)δ ppm 0.89 (m, J=6.94 Hz, 3 H) 1.21 (m, J=6.64 Hz, 3 H) 1.34 (m, 6 H)1.50 (m, 2 H) 3.32 (ddd, J=18.37, 6.06, 1.76 Hz, 1 H) 3.67 (ddd,J=18.37, 12.02, 3.32 Hz, 1 H) 4.08 (m, 1 H) 5.73 (dt, J=12.02, 6.06 Hz,1 H) 6.48 (dd, J=8.01, 5.67 Hz, 1 H) 7.08 (m, 3 H) 7.11 (m, 1 H) 7.16(m, 2 H) 7.25 (m, 1 H) 466 36

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclopropylamide 1H NMR (300 MHz, DMSO-d₆) δ ppm 0.63(m, 4 H) 2.77 (m, 1 H) 3.06 (dd, J=18.02, 5.57 Hz, 1 H) 3.64 (dd,J=18.02, 11.86 Hz, 1 H) 5.81 (dd, J=11.86, 5.57 Hz, 1 H) 7.13 (d, J=8.50Hz, 2 H) 7.26 (m, 3 H) 7.42 (d, J=2.34 Hz, 1 H) 7.49 (d, J=8.64 Hz, 1 H)8.36 (d, J=4.39 Hz, 1 H) 408 37

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclopentylamide 1H NMR (400 MHz, CHLOROFORM-d₆) δ ppm1.44–1.75 (m, 6 H) 2.06 (td, J=13.09, 5.86 Hz, 2 H) 3.32 (dd, J=18.37,6.25 Hz, 1 H) 3.66 (dd, J=18.37, 12.11 Hz, 1 H) 4.31 (m, 1 H) 5.73 (dd,J=12.11, 6.25 Hz, 1 H) 6.62 (d, J=7.82 Hz, 1 H) 7.06 (m, 3 H) 7.12 (s, 1H) 7.17 (m, 2 H) 7.25 (m, 1 H) 436 38

Azocan-1-yl-[5-(4-chloro-phenyl)-1- (2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-methanone 1H NMR (400 MHz, CHLOROFORM-d₆) δ ppm 1.61(m, 6 H) 1.82 (m, 4 H) 3.37 (dd, J=17.98, 5.86 Hz, 1 H) 3.62 (m, 2 H)3.72 (dd, J=17.98, 11.72 Hz, 1 H) 3.87 (m, 2 H) 5.65 (dd, J=11.72, 5.86Hz, 1 H) 7.06 (m, 4 H) 7.17 (m, 2 H) 7.25 (m, 1 H) 464 39

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(1,3-dihydro-isoindol-2-yl)- methanone 1H NMR (400 MHz,CHLOROFORM-d₆) δ ppm 3.44 (dd, J=17.98, 6.25 Hz, 1 H) 3.78 (dd, J=17.98,12.11 Hz, 1 H) 4.98 (d, J=3.13 Hz, 2 H) 5.24 (d, J=16.02 Hz, 1 H) 5.32(d, J=16.02 Hz, 1 H) 5.70 (dd, J=12.11, 6.25 Hz, 1 H) 7.10 (m, 3 H) 7.17(m, 3 H) 7.32 (m, 5 H) 470 40

Azetidin-1-yl-[5-(4-chloro-phenyl)- 1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-methanone 1H NMR (300 MHz, DMSO-d₆) δ ppm 2.26 (m,J=7.58, 2 H) 3.01 (dd, J=18.02, 6.30 Hz, 1 H) 3.64 (dd, J=18.02, 12.01Hz, 1 H) 3.99 (ddd, J=17.43, 4.10, 3.85 Hz, 2 H) 4.38 (q, J=7.67 Hz, 1H) 4.53 (m, 1 H) 5.77 (dd, J=12.01, 6.30 Hz, 1 H) 7.17 (m, 2 H) 7.27 (m,4 H) 7.46 (d, J=2.20 Hz, 1 H) 408 41

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-carboxylic acid cyclohexylamide 450 42

[1,4′]Bipiperidinyl-1′-yl-[5-(4-chloro- phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]- methanone 519 43

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(4-methyl-piperazin-1-yl)- methanone 1H NMR (300 MHz, DMSO-d₆) δ ppm2.18 (s, 3 H) 2.35 (m, 4 H) 3.11 (dd, J=17.80, 6.96 Hz, 1 H) 3.52 (m, 1H) 3.61 (m, 1 H) 3.70 (dd, J=17.80, 11.64 Hz, 1 H) 3.87 (m, 2 H) 5.71(dd, J=11.64, 6.96 Hz, 1 H) 7.22 (m, 4 H) 7.31 (m, 2 H) 7.48 (d, J=1.61Hz, 1 H) 451 44

4-[5-(4-Chloro-phenyl)-1-(2,4-di-chloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carbonyl]-piperazine-1-carboxylic acid ethyl ester 509 45

[5-(4-Chloro-phenyl)-1-(2,4-di- chloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(3,4-dihydro-1H-isoquinolin-2- yl)-methanone 484 46

[5-(4-Chloro-phenyl)-1-(2,4-di- chloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(2-methyl-piperidin-1-yl)- methanone 450 47

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclohexyl-methyl- amide 1H NMR (300 MHz, DMSO-d₆) δ ppm1.22 (m, 4 H) 1.57 (m, 3 H) 1.73 (m, 3 H) 2.97 (s, 3 H) 3.10 (dd,J=17.80, 7.03 Hz, 1 H) 3.71 (dd, J=17.80, 11.64 Hz, 1 H) 4.28 (m, 1 H)5.71 (m, 1 H) 7.22 (m, 4 H) 7.30 (m, 2 H) 7.48 (m, 1 H) 464 48

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,4-dioxo-imidazol idin-1-yl)-amide 466 49

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclododecylamide 1H NMR (300 MHz, DMSO-d₆) δ ppm 1.29(m, 20 H) 1.63 (m, 2 H) 3.06 (dd, J=18.09, 5.93 Hz, 1 H) 3.65 (dd,J=18.09, 11.86 Hz, 1 H) 4.04 (m, 1 H) 5.81 (dd, J=11.86, 5.93 Hz, 1 H)7.14 (m, 2 H) 7.28 (m, 3 H) 7.43 (d, J=2.34 Hz, 1 H) 7.50 (d, J=8.79 Hz,1 H) 8.00 (d, J=8.79 Hz, 1 H) 534 50

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid diisopropylamide 1H NMR (300 MHz, DMSO-d₆) δ ppm 1.20(m, 6 H) 3.09 (dd, J=17.65, 6.66 Hz, 1 H) 3.60 (m, 1 H) 3.67 (dd,J=17.65, 11.43 Hz, 1 H) 4.52 (m, 1 H) 5.69 (dd, J=11.43, 6.66 Hz, 1 H)7.20 (m, 4 H) 7.32 (m, 2 H) 7.46 (d, J=2.05 Hz, 1 H) 452 51

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid dimethylamide 396 52

(4-Benzyl-piperazin-1-yl)-[5-(4- chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]- methanone 527 53

1-[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carbonyl]-pyrrolidine-2-carboxylic acid 466 54

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-morpholin-4-yl-methanone 1H NMR (300 MHz, DMSO-d₆) δ ppm 3.12 (dd,J=17.87, 6.37 Hz, 1 H) 3.62 (m, 6 H) 3.72 (dd, J=17.87, 11.06 Hz, 1 H)3.93 (m, 2 H) 5.71 (dd, J=11.06, 6.37 Hz, 1 H) 7.22 (m, 4 H) 7.31 (m, 2H) 7.48 (s, 1 H) 438 55

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cyclohexyl-isopropyl- amide 492 56

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(6,7-dihydro-4H-thieno[3,2-c]- pyridin-5-yl)-methanone 490 57

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (3-methyl-cyclohexyl)- amide 464 58

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (1,7,7-trimethyl- bicyclo[2.2.1]hept-2-yl)-amide 504 59

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(5-ethyl-2-methyl-piperidin-1- yl)-methanone 478 60

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide hydrochloride 1H NMR (300 MHz,METHANOL-d₆) δ ppm 1.68 (m, 2 H) 1.92–2.03 (m, 4 H) 3.24 (dd, J=18.02,6.52 Hz, 1 H) 3.49 (br. s,4 H) 3.76 (dd, J=18.02, 12.52 Hz, 1 H) 5.95(dd, J=12.52, 6.52 Hz, 1 H) 7.14 (d, J=8.50 Hz, 2 H) 7.21 (dd, J=8.72,2.42 Hz, 1 H) 7.40 (m, 3 H) 7.37 (d, J=2.42 Hz, 1 H) 495 61

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid pyrrolidin-1-ylamide 482 62

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,6-dimethyl- piperidin-1-yl)-amide 524 63

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro-cyclopenta- [c]pyrrol-2-yl)-amide 1H NMR (300MHz, CHLOROFORM-d₆) δ ppm 1.54–1.85 (m, 6 H) 2.91 (br. s,2 H) 3.25 (dd,J=18.16, 6.08 Hz, 1 H) 3.29 (br, s,2 H) 3.68 (dd, J=18.16, 12.52 Hz, 1H) 3.79 (br, s, 2 H) 5.81 (dd, J=12.52, 6.08 Hz, 1 H) 6.98 (d, J=8.50Hz, 2 H) 7.09 (dd, J=8.64, 2.34 Hz, 1 H) 7.20–7.25 (m, 2 H) 7.34 (d,J=8.35 Hz, 2 H) 9.04 (br. s,1 H) 522 64

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (4-cyclopentyl- piperazin-1-yl)-amide 565 65

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (1H,3H-benzo[de]- isoquinolin-2-yl)-amide 580 66

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,3-dihydro-indol-1- yl)-amide hydrochloride 1H NMR(300 MHz, METHANOL-d₆) δ ppm 3.05 (t, J=7.98 Hz, 2 H) 3.28 (dd, J=18.09,5.86 Hz, 1 H) 3.64 (t, J=8.50 Hz, 2 H) 3.77 (dd, J=18.09, 12.16 Hz, 1 H)5.93 (dd, J=12.16, 5.86 Hz, 1 H) 6.71 (d, J=7.76 Hz, 1 H) 6.84 (t,J=7.40 Hz, 1 H) 7.07–7.21 (m, 5 H) 7.31 (d, J=2.34 Hz, 1 H) 7.44 (d,J=8.64 Hz, 1 H) 7.40 (d, J=8.50 Hz, 2 H) 529 67

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 498 68

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azepin-1-ylamide 1H NMR (300 MHz, CHLOROFORM-d₆) δ ppm1.75 (m, 6 H) 2.91 (br. s, 4 H) 2.00 (br. s, 4 H) 3.26 (dd, J=18.16,6.15 Hz, 1 H) 3.71 (dd, J=18.16, 12.45 Hz, 1 H) 3.65 (br. s, 4 H) 5.82(dd, J=12.45, 6.15 Hz, 1 H) 6.97 (d, J=8.35 Hz, 2 H) 7.10 (d, J=2.20 Hz,1 H) 7.16–7.22 (m, 1 H) 7.24 (d, J=2.20 Hz, 1 H) 7.35 (d, J=8.50 Hz, 2H) 510 69

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid propylamide 410 70

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid tert-butylamide 424 71

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-morpholin-4-yl- ethyl)-amide 481 72

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid butylamide 424 73

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (3-dimethylamino- propyl)-amide 453 74

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(3,6-dihydro-2H-pyridin-1-yl)- methanone 434 75

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(5,6-dihydro-4H-pyrimidin-1-yl)- methanone 435 76

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (1,2,3,4-tetrahydro- naphthalen-1-yl)-amide 498 77

Azocan-1-yl-[5-(4-chloro-phenyl)-1- (2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-methanone 464 78

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(2,3-dihydro-1H-cyclopenta[b]- indol-4-yl)-methanone 508 79

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (3,5-dimethyl- [1,2,4]triazol-4-yl)-amide 463 80

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(2,3-dimethyl-morpholin-4-yl)- methanone 466 81

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)- methanone 484 82

5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 1H NMR (300MHz, METHANOL-d₆) δ ppm 1.36 (m, 4 H) 1.75 (m, 2 H) 2.02 (m, 2 H) 3.24(dd, J=5.71, 18.08 Hz, 1 H) 3.50 (m, 1H 3.70 (dd, J=18.10, 12.01 Hz, 1H) 3.74 (m, 1 H) 5.91 (dd, J=12.01, 5.71 Hz, 1 H)7.12–7.32 (m, 6 H) 7.45(t, J=8.28 Hz, 1 H) 466 83

5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 1H NMR (300MHz, METHANOL-d₆) δ ppm 1.36 (m, 4 H) 1.75 (m, 2 H) 2.02 (m, 2 H) 3.24(dd, J=5.71, 18.08 Hz, 1 H) 3.50 (m, 1 H) 3.70 (dd, J=18.10, 12.01 Hz, 1H) 3.74 (m, 1 H) 5.91 (dd, J=12.01, 5.71 Hz, 1 H) 7.12–7.32 (m, 6 H)7.45 (t, J=8.28 Hz, 1 H) 466 84

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-cyclohexyl-ethyl)- amide 478 85

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(dodecahydro-carbazol-9-yl)- methanone 530 86

[5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-(4-propyl-piperidin-1-yl)- methanone 478 87

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-cyclopentyl- ethyl)-amide 464 88

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid bicyclo[2.2.1]hept- 2-ylamide 462 89

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid pyrrolidin-1- ylamide 421 90

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,6-dimethyl- piperidin-1-yl)-amide 463 91

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro- cyclopenta[c]pyrrol-2-yl)-amidehydrochloride 1H NMR (300 MHz, DMSO-d₆) δ ppm 1.48 (d, J=8.20 Hz, 2 H)1.52–1.68 (m, 4 H) 2.66 (br. s, 2 H) 2.87 (m, 2 H) 3.11 (dd, J=18.02,6.30 Hz, 1 H) 3.54 (m, 2 H) 3.66 (dd, J=18.02, 12.01 Hz, 1 H) 5.85 (dd,J=12.01, 6.30 Hz, 1 H) 7.06 (t, J=8.79 Hz, 2 H) 7.16–7.24 (m, 2 H) 7.30(dd, J=8.72, 2.27 Hz, 1 H) 7.47 (m, 2 H) 10.58 (br. s, 1 H) 461 91A

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro- cyclopenta[c]pyrrol-2-yl)-amide 92

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (4-cyclopentyl- piperazin-1-yl)-amide 504 93

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (1H,3H-benzo[de]- isoquinolin-2-yl)-amide 519 94

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,3-dihydro-indol- 1-yl)-amide 469 95

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 437 96

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azepan-1-ylamide 1H NMR (300 MHz, CHLOROFORM-d₆) δppm1.75 (br. s, 4 H) 2.00 (br. s, 4 H) 3.28 (dd, J=18.16, 6.08 Hz, 1 H)3.68 (dd, J=18.16, 12.38 Hz, 1 H) 3.68 (br. s, 4 H) 5.84 (dd, J=12.38,6.08 Hz, 1 H) 6.90 (t, J=8.57 Hz, 2 H) 7.08 (m, 3 H) 7.14–7.19 (m, 1 H)7.24 (d, J=2.20 Hz, 1 H) 449 97

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide 543 98

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid pyrrolidin-1-ylamide 529 99

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,6-dimethyl- piperidin-1-yl)-amide 571 100

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro- cyclopenta[c]pyrrol-2-yl)-amide 569 101

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (4-cyclopentyl- piperazin-1-yl)-amide 612 102

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (1H,3H-benzo[de]- isoquinolin-2-yl)-amide 627 103

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,3-dihydro-indol-1- yl)-amide 577 104

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 545 105

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azepan-1-ylamide 557 106

1-(2,4-Dichloro-phenyl)-5-(4-meth- oxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid piperidin-1- ylamide hydrochloride 1H NMR (300 MHz,CHLOROFORM-d₆) δ ppm 1.67 (br. s, 2 H) 2.10 (br. s, 4 H) 3.25 (dd,J=18.02, 6.01 Hz, 1 H) 3.64 (dd, J=18.02, 12.60 Hz, 1 H) 3.72 (s, 3 H)3.89 (br. s, 4 H) 5.85 (dd, J=12.60, 6.01 Hz, 1 H) 6.72 (d, J=8.79 Hz, 2H) 7.00 (d, J=8.64 Hz, 2 H) 7.07 (dd,J=8.64, 2.20 Hz, 1 H) 7.22 (d,J=8.64 Hz, 1H) 7.22 (d, J=2.20 Hz, 1 H) 9.63 (br. s, 1 H) 447 107

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid pyrrolidin-1-ylamide 433 108

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid (2,6-dimethyl-piperidin-1-yl)-amide 475 109

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid (hexahydro-cyclo-penta[c]pyrrol-2-yl)-amide hydrochloride 1H NMR (300 MHz, CHLOROFORM-d₆)δ ppm 1.61–1.91 (m, 6 H) 2.96 (br. s, 2 H) 3.27 (dd, J=18.09, 5.86 Hz, 1H) 3.49 (m, 2 H) 3.64 (dd, J=18.09, 12.60 Hz, 1 H) 3.72 (s, 3 H) 3.90(br. s, 2 H) 5.82 (dd, J=12.60, 5.86 Hz, 1 H) 6.71 (d, J=8.64 Hz, 2H) 7.00 (d, J=8.64 Hz, 2 H) 7.06 (dd, J=8.72, 2.27 Hz, 1 H) 7.21 (m, 2H) 9.25 (br. s, 1 H) 473 109A

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid (hexahydro-cyclo-penta[c]pyrrol-2-yl)-amide 110

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid (4-cyclopentyl-piperazin-1-yl)-amide 516 111

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid (1H,3H-benzo[de]-isoquinolin-2-yl)-amide 531 112

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid(2,3-dihydro-indol- 1-yl)-amide hydrochloride 481 113

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid morpholin-4-ylamide 449 114

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid azepan-1-ylamidehydrochloride 1H NMR (300 MHz, METHANOL-d₆) δ ppm 1.77 (br. s, 4 H) 1.98(br. s, 4 H) 3.27 (dd, J=6.15 Hz, 1 H) 3.63 (m, 5 H) 3.70 (s, 3 H) 5.90(dd, J=12.45, 6.15 Hz, 1 H) 6.76 (d, J=8.64 Hz, 2 H) 7.16 (dd, J=8.64,2.20 Hz, 1 H) 7.10 (d, J=8.64 Hz, 2 H) 7.33 (m, 2 H) 461 115

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid methyl ester 383 116

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid methyl ester 427 117

1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid methyl ester 367 118

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid methyl ester 379119

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid methyl ester 475 120

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid ethyl ester 397 121

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid ethyl ester 441 122

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid ethyl ester 381 123

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid ethyl ester 489 124

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid ethyl ester 393125

1-(2,4-Dichloro-phenyl)-5-(4-iodo- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid 461 126

1-(2,4-Dichloro-phenyl)-5-(4- fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid 353 127

1-(2,4-Dichloro-phenyl)-5-(4-meth-oxy-phenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid 365 128

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid 413 129

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid 369 130

5-(4-Bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cycloheptlamide 1H NMR (300 MHz, METHANOL-d₆) δ ppm1.49–1.78 (m, 10 H) 1.95 (br. s, 2 H) 3.21 (dd, J=18.09, 5.79 Hz, 1 H)3.67 (dd, J=18.09, 12.08 Hz, 1 H) 3.99 (m, 1 H) 5.86 (dd, J=12.08, 5.79Hz, 1 H) 7.09 (d, J=8.50 Hz, 2 H) 7.15 (dd, J=8.79, 2.34 Hz, 1 H) 7.30(d, J=2.34 Hz, 1 H) 7.33–7.44 (m, 3 H) 508 131

5-(4-Fluorophenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cycloheptlamide 1H NMR (300 MHz, DMSO-d₆) δ ppm1.36–1.67 (m, 10 H) 1.72–1.87 (m, 2 H) 3.05 (dd, J=18.02, 5.64 Hz, 1 H)3.63 (dd, J=18.02, 11.79 Hz, 1 H) 3.79–3.92 (m, J=8.95, 1 H) 5.80 (dd,J=11.79, 5.64 Hz, 1 H) 7.04 (t, J=8.79 Hz, 2 H) 7.12–7.18 (m, 2 H) 7.26(dd, J=8.79, 2.34 Hz, 1 H)  7.43 (d, J=2.34 Hz, 1 H) 7.50 (d, J=8.79 Hz,1 H) 8.10 (d, J=8.20 Hz, 1 H) 448 132

5-(4-methoxyphenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cycloheptlamide 460 133

5-(4-hydroxyphenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cycloheptlamide 412 134

5-(4-iodophenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid cycloheptlamide 522 135

1-(2,4-Dichloro-phenyl)-5-(4-fluoro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide hydrochloride 1H NMR (300 MHz,DMSO-d₆) δ ppm 1.42 (br. s, 2 H) 1.72 (br. s, 4 H) 3.08 (dd, J=18.02,6.23 Hz, 1 H) 3.14 (br. s, 4 H) 3.69 (dd, J=18.02, 12.08 Hz, 1 H) 5.84(dd, J=12.08, 6.23 Hz, 1 H) 7.06 (t, J=8.79 Hz, 2 H) 7.20 (dd, J=8.72,5.49 Hz, 2 H) 7.30 (dd, J=8.72, 2.42 Hz, 1 H) 7.40–7.53 (m, 2 H) 10.54(br. s, 1 H) 435 136

1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide 462 137

(R)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide 462 138

(S)-1-(2,4-dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide 462 139

(R)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 466 140

(S)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 466 141

(R)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 466 142

(S)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 466 143

1-(2,4-dichlorophenyl)-5-(4- fluorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 450 144

1-(2,4-dichlorophenyl)-5-(4- iodophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 558 145

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azocan-1-ylamide hydrochloride 1H NMR (300 MHz,METHANOL-d₆) δ ppm 1.76 (br. s, 6 H) 2.01 (br. s, 4 H) 3.26 (dd,J=18.02, 6.52 Hz, 1 H) 3.65 (m, 4 H) 3.76 (dd, J=18.02, 12.52 Hz, 1 H)5.96 (dd, J=12.52, 6.52 Hz, 1 H) 7.16–7.28 (m, 5 H) 7.40 (d, J=8.64 Hz,1 H) 7.37 (d, J=2.34 Hz, 1 H) 479 146

5-(4-bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azocan-1-ylamide 523 147

5-(4-fluoro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azocan-1-ylamide 463 148

5-(4-methoxy-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azocan-1-ylamide 1H NMR (300 MHz, CHLOROFORM-d₆) δ ppm1.53–1.62 (m, 2 H) 1.68 (br. s, 8 H) 3.10 (m, 4 H) 3.34 (dd, J=18.31,6.01 Hz, 1 H) 3.64 (dd, J=18.31, 12.01 Hz, 1 H) 3.72 (s, 3 H) 5.68 (dd,J=12.01, 6.01 Hz, 1 H) 6.70 (d, J=8.64 Hz, 2 H) 7.03 (m, 3 H) 7.08–7.13(m, 1 H) 7.23 (d, J=2.34 Hz, 1 H) 7.93 (br. s, 1 H) 475 149

5-(4-hydroxy-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azocan-1-ylamide hydrochloride 461 150

5-(4-iodo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azocan-1-ylamide 571 151

N-((1S,2S)-2-(benzyloxy)cyclohexyl)- 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 556 152

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (4-oxo-piperidin-1- yl)-amide 465 153

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (3,6-dihydro-2H- pyridin-1-yl)-amide 1H NMR (250 MHz,DMSO-d₆) δ ppm 2.20 (br. s, 2 H) 2.96 (t, J=5.63 Hz, 2 H) 3.08 (dd,J=17.98, 5.76 Hz, 1 H) 3.37 (br. s, 2 H) 3.67 (dd, J=17.98, 11.80 Hz, 1H) 5.58–5.74 (m, 2 H) 5.81 (dd, J=11.80, 5.76 Hz, 1 H) 7.13–7.24 (m, 2H) 7.30 (d, J=8.23 Hz, 3 H) 7.51 (d, J=8.78 Hz, 1 H) 7.45 (d, J=2.47 Hz,1 H) 9.41 (s, 1 H) 449 154

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (3-hydroxy-piperidin- 1-yl)-amide 1H NMR (300 MHz,DMSO-d₆) δ ppm 1.05 (d, J=10.26 Hz, 1 H) 1.43 (d, J=10.55 Hz, 1 H)1.52–1.82 (m, 2 H) 2.57 (m, 1 H) 2.83 (m, 1 H) 3.04 (m, 2 H) 3.41–3.70(m, 2 H) 4.75 (t, J=3.66 Hz, 1 H) 5.78 (dd, J=11.57, 5.42 Hz, 1 H) 7.14(d, J=8.20 Hz, 2 H) 7.28 (d, J=7.91 Hz, 3 H) 7.37–7.57 (m, 2 H) 9.33 (s,1 H) 467 155

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (4-hydroxy-piperidin- 1-yl)-amide 1H NMR (250 MHz,CHLOROFORM-d₆) δ ppm 1.91 (m, 2 H) 2.08 (m, 2 H) 2.89 (m, 2 H) 3.15 (m,2 H) 3.40 (dd, J=18.39, 6.31 Hz, 1 H) 3.76 (dd, J=18.39, 12.08 Hz, 1 H)3.91 (d, J=3.57 Hz, 1 H) 5.80 (dd, J=12.08, 6.31 Hz, 1 H) 7.09–7.20 (m,4 H) 7.24 (m, 2 H) 7.33 (m, 1 H) 7.55 (s, 1 H) 467 156

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-hydroxy-piperidin- 1-yl)-amide 467 157

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (3,4-dihydro-2H- pyridin-1-yl)-amide 449 158

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-1-ylamide 502 159

(R)-5-(4-Chloro-phenyl)-1-(2,4- dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-1-ylamide 502 160

(S)-5-(4-Chloro-phenyl)-1-(2,4- dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-1-ylamide 502 161

5-(4-bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-1-ylamide 546 162

5-(4-fluoro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-1-ylamide 486 163

5-(4-methoxy-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-1-ylamide 498 164

5-(4-hydroxy-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-1-ylamide 484 165

5-(4-iodo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-1-ylamide 594 166

5-(4-Chloro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-2-ylamide 502 167

5-(4-bromo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-2-ylamide 546 168

5-(4-fluoro-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-2-ylamide 486 169

5-(4-methoxy-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-2-ylamide 498 170

5-(4-hydroxy-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-2-ylamide 484 171

5-(4-iodo-phenyl)-1-(2,4-dichloro- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid adamantan-2-ylamide 594 172

1-(2,4-Dichloro-phenyl)-5-(4-hydroxy- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide hydrochloride 1H NMR (300 MHz,METHANOL-d₆) δ ppm 1.69 (br. s, 2 H) 2.00 (br. s, 4 H) 3.24 (dd,J=17.94, 6.23 Hz, 1 H) 3.55 (br. s, 4 H) 3.69 (dd, J=17.94, 12.38 Hz, 1H) 5.86 (dd, J=12.38, 6.23 Hz, 1 H) 6.61 (d, J=8.50 Hz, 2 H) 7.00 (d,J=8.50 Hz, 2 H) 7.17 (dd, J=8.64, 2.20 Hz, 1 H) 7.26–7.38 (m, 2 H) 433173

1-(2,4-Dichloro-phenyl)-5-(4-hydroxy- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azepan-1-ylamide hydrochloride 1H NMR (300 MHz, DMSO-d₆)δ ppm 0.81 (d, J=7.18 Hz, 3 H) 1.59 (br. s, 4 H) 1.78 (br. s, 4 H) 3.36(br. s, 4 H) 3.76 (dq, J=11.28, 7.18 Hz, 1 H) 5.81 (d, J=11.28 Hz, 1 H)6.59 (d, J=8.50 Hz, 2 H) 6.89 (d, J=8.50 Hz, 2 H) 7.31 (dd, J=8.79, 2.34Hz, 1 H) 7.49 (d, J=2.34 Hz, 1 H) 7.56 (d, J=8.64 Hz, 1 H) 9.43 (br. s,1 H) 10.90 (br. s, 1 H) 447 174

1-(2,4-Dichloro-phenyl)-5-(4-hydroxy- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro-cyclo- penta[c]pyrrol-2-yl)-amidehydrochloride 1H NMR (300 MHz, METHANOL-d₆) ppm 1.68 (br. s, 2 H) 1.81(br. s, 4 H) 2.98 (br. s, 2 H) 3.06–3.21 (m, 2 H) 3.26 (dd, J=18.02,6.30 Hz, 1 H) 3.71 (dd, J=18.02, 12.45 Hz, 1 H) 4.06 (m, 2 H) 5.88 (dd,J=12.45, 6.30 Hz, 1 H) 6.63 (d, J=8.64 Hz, 2 H) 7.02 (d, J=8.64 Hz, 2 H)7.18 (dd, J=8.64, 2.34 Hz, 1 H) 7.37 (d, J=2.20 Hz, 1 H) 7.34 (d, J=8.79Hz, 1 H) 459 175

1-(2,4-Dichloro-phenyl)-5-(4-hydroxy- phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,3-dihydro-indol- 1-yl)-amide hydrochloride 467 176

(R)-5-(4-Chloro-phenyl)-1-(2,4- dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azocan- 1-ylamide hydrochloride 1H NMR (300MHz, METHANOL-d₆) δ ppm 1.76 (br. s, 6 H) 2.01 (br. s, 4 H) 3.26 (dd,J=18.02, 6.52 Hz, 1 H) 3.65 (m, 4 H) 3.76 (dd, J=18.02, 12.52 Hz, 1 H)5.96 (dd, J=12.52, 6.52 Hz, 1 H) 7.16–7.28 (m, 5 H) 7.40 (d, J=8.64 Hz,1 H) 7.37 (d, J=2.34 Hz, 1 H) 479 177

(S)-5-(4-Chloro-phenyl)-1-(2,4- dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid azocan- 1-ylamide hydrochloride 1H NMR (300MHz, METHANOL-d₆) δ ppm 1.76 (br. s, 6 H) 2.01 (br. s, 4 H) 3.26 (dd,J=18.02, 6.52 Hz, 1 H) 3.65 (m, 4 H) 3.76 (dd, J=18.02, 12.52 Hz, 1 H)5.96 (dd, J=12.52, 6.52 Hz, 1 H) 7.16–7.28 (m, 5 H) 7.40 (d, J=8.64 Hz,1 H) 7.37 (d, J=2.34 Hz, 1 H) 479 184

(S)-5-(4-Chloro-phenyl)-1-(2,4- dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride 477 188

(R)-5-(4-Chloro-phenyl)-1-(2,4- dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide 477 193

5-(4-Chloro-phenyl)-1-(2,4- dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride 477 196

(R)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 466 197

(S)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 466 198

(R)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 466 199

(S)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 466 200

5-(4-bromophenyl)-1-(2,4- dichlorophenyl)-N-((1S,2S)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 510 201

5-(4-bromophenyl)-1-(2,4- dichlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 510 202

1-(2,4-dichlorophenyl)-N-(1S,2S)-2- hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 462 203

1-(2,4-dichlorophenyl)-N-(1R,2R)-2- hydroxycyclohexyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H- pyrazole-3-carboxamide 462 178N-((1R,2R)-2-(benzyloxy)cyclohexyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide[M + H]⁺ = 556 1791-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [M + H]⁺ = 469 1801-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid [M + H]⁺ = 351 181(R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [M + H]⁺ = 485 182(S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [M + H]⁺ = 485 183(S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide hydrochloride [M + H]⁺ = 465 184(S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride [M + H]⁺ =477 185(S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide [M + H]⁺ = 465 186(S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid cycloheptylamide [M + H]⁺ = 464 187(R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide hydrochloride [M + H]⁺ = 465 188(R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide [M + H]⁺ = 477 189(R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid cycloheptylamide [M + H]⁺ = 464 190(R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide [M + H]⁺ = 485 1915-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid cycloheptylmethyl-amide [M + H]⁺ = 478 1925-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,6-dimethyl-piperidin-1-yl)-amide hydrochloride [M + H]⁺ = 4791935-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride [M + H]⁺ =477 1945-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid pyrrolidin-1-ylamide hydrochloride [M + H]⁺ = 437 195[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(4-methyl-piperazin-1-yl)-methanonehydrochloride [M + H]⁺ = 451 60A5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid piperidin-1-ylamide 66A5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide 82A5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2-(R)-hydroxy-cyclohexyl)-amide 83A5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2-(S)-hydroxy-cyclohexyl)-amide 91A1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide 106A1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid piperidin-1-ylamide 109A1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide 112A1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide 114A1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamideI. In-vitro Determination of Affinity to CB1/CB2-Receptors

The binding data for some of the inventive compounds was obtained asdescribed above in the section pharmacological methods, part I, and isgiven in the following table (table 1).

TABLE 1 Compound according to Inhibition Inhibition [%], example IC₅₀[nM] [%], 10⁻⁷ M 10⁻⁸ M  7 146 71.2 −12.8  8 21.9 −8.2  11 630  12 250 13 31.8 14.3  16 26.3  18 25.1  22 79.4  23 39.8  27 117 50.7 32.9 29 >1000  31 >1000  32 84 52.7 12  34 56.2  37 280  41 3.4 −5.2  52251.2  57 39.8  60 27  60A 44 65.8 33.3  63 25.1  64 562.3  66 100  6839.8  69 354.8  72 19.6 −10.2  73 −18.9 15.7  74 794.3  75 >1000  76398.1  80 501.2  81 707.9  87 15.2 −2.4  91 47 79.1 43  91A 84 75.3 34.9 96 56 74.8 43.3 106 32 76.1 23.4  106A 20 109 16 80.6 44  109A 15 74.233.5 112 106 61.8 46.3 114 24 68.7 47.6  114A 18 79.3 41.4 115 −4.3 1.9120 7.1 −4.1 127 7.8 7.4 130 52 67.7 33.1 131 115 70.2 42.9 132 37.818.2 133 31.4 13.8 135 83 78.5 40.2 145 57.6 12.3 146 12 71.8 35.2 14754 63.4 24.0 148 80.3 56.1 151 32 82.3 67.5 172 1.4 5.6 176 71.3 29.5177 22.2 −5.4 178 119 58 41.2 179 33.9 11.5 180 9.3 4.7 181 24 50.6 33.7182 31.7 18.8 183 31.9 3.2 184 24.8 5.7 185 34.1 −11.6 186 28.1 3.2 1877.9 188 15.8 189 15.8 190 100 191 67.4 30.2 192 501.2 193 70.8 194 41.722.9 195 5.8 4.7

The antagonism of the pyrazoline compounds of general formula I to theCB1-receptor was determined according to the method described inPharmacological methods, part V (table 2).

TABLE 2 Compound according to example Antagonism [%]  8 54  9 53 10 11912 78 15 6 17 65 18 78 20 61 21 66 22 62 23 91 24 27 25 7 26 52 27 31 2863 30 54 33 2 34 60 35 68 36 −5 37 81 38 45 39 62 40 32 41 69 42 −13 4325 44 39 45 59 46 53 47 28 49 14 50 18 51 21 53 14 54 46 55 30 56 44 5781 58 47 59 60 61 75 62 67 63 119 64 63 66 86 67 52 68 98 74 44 75 42 7657 80 56 81 20 106A 112 115  23 120  30 126  30 128  18 191  82 192  63193  115 194  82

1. A substituted pyrazoline compound of formula I,

wherein R¹ represents a phenyl radical that is substituted with ahydroxy, fluorine, chlorine, bromine or iodine atom or a —O—CH₃-group inthe para-(4-)-position of the phenyl radical; R² represents a(2,4)-dichloro-phenyl radical; R³ represents a —NR⁴R⁵ moiety; R⁴represents a hydrogen atom; R⁵ represents a radical selected from thegroup consisting of adamantyl, bicyclo[2.2.1]heptyl,bicyclo[3.1.1]heptyl, (1,7,7)-trimethyl-bicyclo[2.2.1]heptyl,[1,2,3,4]-tetrahydronaphthyl, cyclononyl, cyclodecyl, cycloundecyl andcyclododecyl; a radical selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl,morpholinyl, azepanyl, diazepanyl and azocanyl, which is bonded via a—(CF₂)—, —(CH₂)—CH₂)— or —(CH₂)—(CH₂)—(CH₂)-group; a substituted radicalselected from the group consisting of cyclopentyl, cyclohexyl andcyloheptyl which is substituted with a —O-Benzyl radical; or a radicalselected from the group consisting of

which is in each case bonded to the pyrazoline compound of formula I inany position of the cyclic part of the aforementioned radicals includingthe NH-groups; optionally in a form of one of its stereoisomers or aracemate or in a form of a mixture of at least two of its stereoisomersin any mixing ratio, or a corresponding N-oxide thereof, or aphysiologically acceptable salt thereof.
 2. A compound according toclaim 1 selected from the group consisting of [10]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide [13]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid [2-(S)-(1-methoxy-1-methyl-ethyl)-pyrrolidin-1-yl]-amide [14]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid [2-(R)-(1-methoxy-1-methyl-ethyl)-pyrrolidin-1-yl]-amide [15]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid [2-(1-methoxy-1-methyl-ethyl)-pyrrolidin-1-yl]-amide [16]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide [21][5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-(4-cyclohexyl-piperazin-1-yl)-methanone[24]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-amide [25]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (1H,3H-benzo[de]isoquinolin-2-yl)-amide [26]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (4-cyclopentyl-piperazin-1-yl)-amide [27]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2-methyl-2,3-dihydro-indol-1-yl)-amide [28]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide [32]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid cyclohexylmethyl-amide [48]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,4-dioxo-imidazolidin-1-yl)-amide [49]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid cyclododecylamide [58]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide [63]5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide [64]5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (4-cyclopentyl-piperazin-1-yl)-amide [65]5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (1H,3H-benzo[de]isoquinolin-2-yl)-amide [66]5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [68]5-(4-Bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-yl-amide [71]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2-morpholin-4-yl-ethyl)-amide [76]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide [84]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2-cyclohexyl-ethyl)-amide [87]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2-cyclopentyl-ethyl)-amide [88]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid bicyclo[2.2.1]hept-2-ylamide [91]1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride [92]1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (4-cyclopentyl-piperazin-1-yl)-amide [93]1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (1H,3H-benzo[de]isoquinolin-2-yl)-amide [94]1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide [96]1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-yl-amide [100]1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide [101]1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (4-cyclopentyl-piperazin-1-yl)-amide [102]1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (1H,3H-benzo[de]isoquinolin-2-yl)-amide [103]1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide [105]1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide; [109]1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride [110]1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (4-cyclopentyl-piperazin-1-yl)-amide [111]1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (1H,3H-benzo[de]isoquinolin-2-yl)-amide [112]1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [114]1-(2,4-Dichloro-phenyl)-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide hydrochloride [145]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azocan-1-ylamide hydrochloride [146]5-(4-bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azocan-1-ylamide [147]5-(4-fluoro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azocan-1-ylamide [148]5-(4-methoxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azocan-1-ylamide [149]5-(4-hydroxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azocan-1-ylamide hydrochloride [150]5-(4-iodo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azocan-1-ylamide [151]N-((1S,2S)-2-(benzyloxy)cyclohexyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide[158]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-1-ylamide [159](R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-l-ylamide [160](S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-1-ylamide [161]5-(4-bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-1-ylamide [162]5-(4-fluoro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-1-ylamide [163]5-(4-methoxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-1-ylamide [164]5-(4-hydroxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-1-ylamide [165]5-(4-iodo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-1-ylamide [166]5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-2-ylamide [167]5-(4-bromo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-2-ylamide [168]5-(4-fluoro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-2-ylamide [169]5-(4-methoxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-2-ylamide [170]5-(4-hydroxy-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-2-ylamide [171]5-(4-iodo-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid adamantan-2-ylamide [173]1-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide hydrochloride [174]1-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride [175]1-(2,4-Dichloro-phenyl)-5-(4-hydroxy-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [176](R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azocan-1-ylamide hydrochloride [177](S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azocan-1-ylamide hydrochloride, [178]N-((1R,2R)-2-(benzyloxy)cyclohexyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide[179]1-(2,4-Dichloro-phenyl)-5-(4-fluoro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [181](R)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [182](S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-yl)-amide hydrochloride [183](S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide hydrochloride [184](S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride [185](S)-5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide [187](R)-5-(4-Chloro-pheny)-1-(2,4-dichloro-pheny)-4,5-dihydro-1H-pyrazole-3-carboxylicacid azepan-1-ylamide hydrochloride [188](R)-5-(4-Chloro-pheny)-1-(2,4-dichloro-pheny)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide [190](R)-5-(4-Chloro-pheny)-1-(2,4-dichloro-pheny)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (2,3-dihydro-indol-1-y)-amide [191]5-(4-Chloro-pheny)-1-(2,4-dichloro-pheny)-4,5-dihydro-1H-pyrazole-3-carboxylicacid cycloheptylmethyl-amide [193]5-(4-Chloro-pheny)-1-(2,4-dichloro-pheny)-4,5-dihydro-1H-pyrazole-3-carboxylicacid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide hydrochloride optionallyin a form of one of its stereoisomers or a racemate or in a form of amixture of at least two of its stereoisomers, in any mixing ratio, or acorresponding N-oxide thereof, or a physiologically acceptable saltthereof.
 3. A process for the preparation of a compound of formula Iaccording to claim 1, characterized in that at least one compound offormula II,

wherein R¹ has the meaning according to claim 1, is reacted with atleast one compound of formula III,

or a corresponding salt thereof, wherein R² has the meaning according toclaim 1, in a reaction medium, optionally in an inert atmosphere,optionally in the presence of at least one acid, to yield at least onecompound of formula IV,

wherein R¹ and R² have the meaning according to claim 1, which isoptionally isolated or purified, and at least one compound of formula IVis reacted with an activating agent in a reaction medium, optionally inan inert atmosphere, to yield at least one compound of formula V,

wherein R¹ and R² have the meaning according to claim 1 and A representsa leaving group, which is optionally purified or isolated, and at leastone compound of formula V is reacted with at least one compound offormula R³—H, wherein R³ has the meaning according to claim 1, in areaction medium, optionally in an inert atmosphere, optionally in thepresence of at least one base selected from the group consisting ofdiisopropylethylamine, triethylamine, pyridine, dimethylaminopyridineand N-methylmorpholine, to yield at least one compound of formula I,wherein R¹, R² and R³ have the meaning according to claim 1, which isoptionally purified or isolated; or at least one compound of formula IVis reacted with at least one compound of formula R³—H, wherein R³represents a —NR⁴R⁵ moiety, wherein R⁴ and R⁵ have the meaning accordingto claim 1, in a reaction medium, in the presence of at least onecoupling agent, optionally in the presence of at least one base, toyield at least one compound of formula I, wherein R¹ and R² have themeaning according to claim 1 and R³ represents a —NR⁴R⁵ moiety, which isoptionally purified or isolated.
 4. A process for the preparation of acompound of formula I according to claim 1, characterized in that atleast one compound of formula R¹—C(═O)—H (formula VII), wherein R¹ hasthe meaning according to claim 1, is reacted with at least one compoundof formula VI,

wherein R′ represents a linear or branched C₁₋₆-alkyl radical, apotassium cation or a sodium cation, in a reaction medium, optionally inan inert atmosphere, optionally in the presence of at least one base, toyield at least one compound of formula II,

wherein R¹ has the meaning according to claim 1, which is optionallypurified or isolated, and at least one compound of formula II is reactedwith an activating agent in a reaction medium, optionally in an inertatmosphere, to yield at least one compound of formula VIII,

wherein R¹ has the meaning according to claim 1 and A represents aleaving group, which is optionally purified or isolated, and at leastone compound of formula VIII is reacted with at least one compound offormula R³—H, wherein R³ has the meaning according to claim 1, in areaction medium, optionally in an inert atmosphere, optionally in thepresence of at least one base selected from the group consisting ofdiisopropylethylamine, triethylamine, pyridine, dimethylaminopyridineand N-methylmorpholine, to yield at least one compound of formula IX,

wherein R¹ and R³ have the meaning according to claim 1, which isoptionally purified or isolated; or at least one compound of formula IIis reacted with at least one compound of formula R³—H, wherein R³represents a —NR⁴R⁵ moiety, wherein R⁴ and R⁵ have the meaning accordingto claim 1, in a reaction medium, in the presence of at least onecoupling agent, optionally in the presence of at least one base, toyield at least one compound of formula IX, wherein R³ represents a—NR⁴R⁵ moiety, which is optionally purified or isolated, and at leastone compound of formula IX is reacted with at least one compound offormula III,

wherein R² has the meaning according to claim 1, in a reaction medium,optionally in an inert atmosphere, optionally in the presence of atleast one acid, to yield at least one compound of formula I, wherein R¹,R² and R³ have the meaning according to claim 1, which is optionallypurified or isolated.
 5. A medicament comprising at least one compoundaccording to claim 1 and at least one physiologically acceptableauxiliary agent.
 6. A compound according to claim 1, wherein saidradical represented by R⁵ is bonded to the pyrazoline compound ofgeneral formula I at the nitrogen atom of the cyclic part of theaforementioned radicals.